Phytoestrogens in human biomatrices including breast milk.
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Breast Neoplasms↗
Biomedical subjects
M C Yu
Publications and source records attributed to M C Yu.
Transcription termination and 3'-End processing of the spliced leader RNA in kinetoplastids.
Addition of a 39-nucleotide (nt) spliced leader (SL) by trans splicing is a basic requirement for all trypanosome nuclear mRNAs. The SL RNA in Leishmania tarentolae is a 96-nt precursor transcript synthesized by a polymerase that resembles polymerase II most closely. To analyze SL RNA genesis, we mutated SL RNA intron structures and sequence elements: stem-loops II and III, the Sm-binding site, and the downstream T tract. Using an exon-tagged SL RNA gene, we examined the phenotypes produced by a second-site 10-bp linker scan mutagenic series and directed mutagenesis. Here we report that transcription is terminated by the T tract, which is common to the 3' end of all kinetoplastid SL RNA genes, and that more than six T's are required for efficient termination in vivo. We describe mutants whose SL RNAs end in the T tract or appear to lack efficient termination but can generate wild-type 3' ends. Transcriptionally active nuclear extracts show staggered products in the T tract, directed by eight or more T's. The in vivo and in vitro data suggest that SL RNA transcription termination is staggered in the T tract and is followed by nucleolytic processing to generate the mature 3' end. We show that the Sm-binding site and stem-loop III structures are necessary for correct 3'-end formation. Thus, we have defined the transcription termination element for the SL RNA gene. The termination mechanism differs from that of vertebrate small nuclear RNA genes and the SL RNA homologue in Ascaris.
Animals↗
Urinary excretion of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in White, African-American, and Asian-American men in Los Angeles County.
Meats, such as beef, pork, poultry, and fish, cooked at high temperatures produce heterocyclic aromatic amines, which have been implicated indirectly as etiological agents involved in colorectal and other cancers in humans. This study examined the urinary excretion of a mutagenic/carcinogenic heterocyclic aromatic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), among 45 African-American, 42 Asian-American (Chinese or Japanese), and 42 non-Hispanic white male residents of Los Angeles who consumed an unrestricted diet. Total PhIP (free and conjugated) was isolated from overnight urine collections, purified by immunoaffinity chromatography, and then quantified by high-pressure liquid chromatography combined with electrospray ionization mass spectrometry. Geometric mean levels of PhIP in Asian-Americans and African-Americans were approximately 2.8-fold higher than in whites. The urinary excretion levels of PhIP were not associated with intake frequencies of any cooked meat based on a self-administered dietary questionnaire, in contrast to our earlier finding (Ji et al., Cancer Epidemiol. Biomark. Prev., 3: 407-411, 1994) of a positive and statistically significant association between bacon intake and the urinary level of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) among this same group of study subjects. Although there is a statistically significant association between urinary levels of PhIP and MeIQx (2-sided P = 0.001), 10 subjects (8%) displayed extreme discordance between urinary PhIP and MeIQx levels. Several factors, including variable contents of heterocyclic aromatic amines in food, enzymic and interindividual metabolic differences, and analytical methodology determine the degree of concordance between the urinary excretion levels of PhIP and MeIQx. Accordingly, urinary excretion levels of a single heterocyclic aromatic amine can only serve as an approximate measure of another in estimating exposure to these compounds in humans consuming unrestricted diets.
Adult↗
Helicobacter pylori infection and risk of gastric cancer in Shanghai, China: updated results based upon a locally developed and validated assay and further follow-up of the cohort.
Infection with Helicobacter pylori has been associated with an increased risk of gastric cancer in low-risk populations. However, our previous results (P. M. Webb et al., Int. J. Cancer, 67: 603-607, 1996) from an ongoing prospective study in Shanghai, China, a relatively high-risk population, failed to show an association between H. pylori infection and the subsequent risk of gastric cancer. That previous study had a relatively short time period of follow-up and the enzyme-linked immunosorbent assay (ELISA) used was based on strains found in Southern England and without validation among the Chinese. Either one of these two factors could have had an impact on the validity of those earlier observations. An ELISA developed and validated among Shanghai residents was used in the present study to reexamine specific antibodies to H. pylori in 188 gastric cancer patients and 548 control subjects. All of the cases of gastric cancer were identified during the first 12 years of follow-up of a cohort of 18,244 men, ages 45-64 years in Shanghai, from whom blood samples were collected at enrollment during 1986-1989. For each cancer case, three cancer-free control subjects were randomly selected from the cohort and matched to the index cases by age (within 2 years), month and year of sample collection, and neighborhood of residence. The Shanghai-based ELISA detected a higher prevalence of serum antibodies to H. pylori than the English-based assay in both gastric cancer cases (86 versus 53%) and control subjects (85 versus 56%). Virtually all of the subjects (98%) who were H. pylori-seropositive by the English-based assay tested positive by the Shanghai-based assay. On the other hand, 73% of gastric cancer cases and 68% of control subjects who were seronegative according to the English-based assay tested positive by the Shanghai-based assay. Using this alternative assay, combined with increased follow-up, our latest data contradict our earlier findings and show a statistically significant association between H. pylori seropositivity and gastric cancer risk (odds ratio, 1.84; 95% confidence interval, 1.08-3.11). We noted an increasing rate of seropositivity among cases as the time interval between cohort enrollment and cancer diagnosis increased. Among subjects followed for 5 or more years after enrollment, the odds ratio for gastric cancer related to H. pylori seropositivity was 3.74 (95% confidence interval, 1.51-9.30).
Antibodies, Bacterial↗
Annual risk of tuberculous infection in Taiwan, 1996-1998.
Tuberculosis is still an important public health issue in Taiwan, and monitoring the trend of annual risk of infection (ARI) with Mycobacterium tuberculosis is essential. In this study, we conducted tuberculin skin tests to estimate the prevalence and annual risk of M. tuberculosis infection in first-grade schoolchildren in Taiwan Province. Because mass bacille Calmette-Guérin (BCG) vaccination programs have been carried out here, only non-BCG-vaccinated students were tested. From September 1996 through June 1998, there were 520,866 registered first-grade elementary school students in Taiwan Province. Of them, 15,147 (2.9%) were non-BCG-vaccinated, as determined by the absence of a BCG scar. All of them were tested for M. tuberculosis infection with 1 tuberculin unit (0.1 mL injection) of purified protein derivative RT23, by means of the Mantoux technique. Among the tested schoolchildren, 430 (2.8%) had a positive tuberculin reaction. Thus, the calculated ARI was 0.44%. The ARI varied in different areas of Taiwan, being highest (1.04%) in Nantou County and lowest (0.14%) in Miaoli and Tainan Counties. The ARI in aboriginal areas (1.16%) was 2.7 times that in nonaboriginal areas (0.42%). Our results indicate that the M. tuberculosis ARI is still high in Taiwan. To achieve the World Health Organization target of less than 0.1% for industrialized countries, we must intensify tuberculosis control programs in Taiwan.
BCG Vaccine↗
Decontamination of human sclera: an in vitro study.
PURPOSE: The human sclera is frequently used in ophthalmic surgeries and must be preserved in disinfectants that prevent its contamination. In this study the efficiency of glycerin, absolute alcohol (ethanol), and benzalkonium chloride (1:5,000) as human sclera disinfectants were compared. METHODS: Fresh human scleras were trephined, the scleral disks divided into three groups and contaminated with Staphylococcus aureus (ATCC 29213), Pseudomonas aeruginosa (ATCC 27853), or Bacillus cereus (ATCC 11778) for 24 h. Thereafter they were transferred to preservation vials each containing glycerin, absolute alcohol, benzalkonium chloride diluted in 70% alcohol (1:5,000) or Trypticase Soy Broth (control), respectively, and stored at room temperature. From each vial, two scleral disks were removed after 1, 2, 3, 4, 7, 10, and 14 days of immersion. Both were plated on blood agar, one being macerated, and both incubated at 37 degrees C for 48 h. RESULTS: Pseudomonas aeruginosa, S. aureus, and B. cereus were recovered from the glycerin-immersed scleral disks until the second, fourth, and fourteenth days, respectively. Bacillus cereus was recovered from those immersed in absolute alcohol until the fourteenth day, whereas disks infected with the other microorganisms and immersed in absolute alcohol presented no growth since the very first day of immersion. Bacillus cereus was recovered from scleral disks immersed in benzalkonium chloride diluted in 70% alcohol (1:5,000) only on the first day. CONCLUSION: Resistant microorganisms can survive in scleral tissue preserved in glycerin and absolute alcohol. We conclude that benzalkonium chloride diluted in 70% alcohol (1:5,000) in vitro is the best disinfectant for human sclera after 24 h.
Bacillus cereus↗
Increased risk of renal cell carcinoma subsequent to hysterectomy.
In etiological studies of renal cell carcinoma, the associations between exogenous hormones, reproductive factors, or gynecological operations have not been well examined. Our aim was to evaluate gender-specific risk factors for renal cell carcinoma using data from a population-based case-control study conducted in Los Angeles, California and to elucidate possible underlying mechanisms. A population-based case-control study involving 422 female renal cell carcinoma patients, ages 25-74 years, and an equal number of sex-, age-, and race-matched neighborhood controls was conducted in Los Angeles, California. Detailed information regarding reproductive history, hysterectomy, use of exogenous estrogens, and other medical and lifestyle factors was collected through in-person interviews. Compared to women with an intact uterus, those who had undergone hysterectomy were at an increased risk for renal cell carcinoma (odds ratio, 1.8; 95% confidence interval, 1.3-2.5). Parity and use of estrogen replacement therapy were no longer risk factors for renal cell carcinoma when hysterectomy was adjusted for in the analysis. No association between renal cell carcinoma and use of oral contraceptives was found. Limited epidemiological data do not support an endocrine explanation for the observed hysterectomy-renal cell cancer association. We conjecture that unintentional injury to the ureter during the surgical procedure, which results in renal cell damage and consequent renal cell proliferation, may be a cause of the increased cancer risk in hysterectomized women.
Adult↗
DNA methylation differences associated with tumor tissues identified by genome scanning analysis.
Most investigations on the role of DNA methylation in cancer have focused on epigenetic changes associated with known tumor suppressor genes. This may have led to an underestimation of the number of CpG islands altered by DNA methylation, since it is possible that a subset of unknown genes relevant to cancer development may preferentially be affected by epigenetic rather than genetic means and would not be identified as familial deletions, mutations, or loss of heterozygosity. We used a recently developed screening procedure (methylation-sensitive arbitrarily primed-polymerase chain reaction to scan genomic DNA for CpG islands methylated in white blood cells (WBCs) and in tumor tissues. DNA methylation pattern analysis showed little interindividual differences in the WBCs and normal epithelium (adjacent to colon, bladder, and prostate cancer cells), but with some tissue-specific differences. Cancer cells showed marked methylation changes that varied considerably between different tumors, suggesting variable penetrance of the methylation phenotype in patients. Direct sequencing of 8 of 45 bands altered in these cancers showed that several of them were CpG islands, and 2 of these sequences were identified in GenBank. Surprisingly, three of the bands studied corresponded to transcribed regions of genes. Thus, hypermethylation of CpG islands in cancer cells is not confined to the promoters of growth regulatory genes but is also found in actively transcribed regions.
Base Sequence↗
Androgen metabolism and prostate cancer: establishing a model of genetic susceptibility.
The prostate is an androgen-regulated organ, which has led to long-standing interest in the role of androgens in prostate carcinogenesis. Although evidence of a hormonal etiology for prostate cancer is strong, it is almost entirely circumstantial. Much of the problem in proving a causal relationship relates to the continued difficulties in reliably measuring human tissue-specific exposure to endogenous steroid hormones. The international and racial-ethnic variations in prostate cancer incidence, combined with the effects of migration on risk patterns, have suggested that whereas environmental factors are likely to be important, genetic factors might also play a central role in determining prostate cancer risk. We are developing a polygenic model of prostate carcinogenesis focused around a series of genes involved in androgen biosynthesis and androgen activation, transport, and metabolism in the prostate. In this developing model, we have initially targeted four genes based on three main criteria: (a) all encode products that play important roles in inducing androgen stimulation in the prostate; (b) all are polymorphic; and (c) all show substantial allelic variation in the polymorphic marker among the racial-ethnic groups of greatest interest in terms of prostate cancer risk. In addition to studying how the polymorphic markers of interest are related to prostate cancer development within and between racial-ethnic groups, we are concurrently evaluating whether genotypic variations correlate in the anticipated direction with biochemical parameters in vitro and in vivo. We summarize the development of this model and the state of knowledge related to each of the genes comprising the current model. We discuss the extent to which the current model can explain demographic variation in prostate cancer risk as well as the potential for future expansion of the model to incorporate environmental risk factors as well as additional genes. The model, when fully developed, can potentially provide a basis for targeting populations for screening interventions and/or preventive strategies aimed at the multigene products or at the genes themselves.
3-Hydroxysteroid Dehydrogenases↗
Single nucleotide resolution of promoter activity and protein binding for the Leishmania tarentolae spliced leader RNA gene.
In Kinetoplastid protozoa, trans-splicing is a central step in the maturation of nuclear mRNAs. In Leishmania, a common 39 nt spliced-leader (SL) is transferred via trans-splicing from the precursor 96 nt SL RNA to the 5' terminus of all known protein-encoding RNAs. In this study, promoter elements of the L. tarentolae SL RNA gene have been identified with respect to transcriptional activity and putative transcription factor binding. We have mapped the essential regions in the SL RNA gene promoter at single nucleotide resolution using both in vivo transcription and in vitro protein/DNA binding approaches. Two regions located upstream of the SL RNA gene were identified: a GN3CCC element at -39 to -33 and a GACN5G element at -66 to -58 were essential for SL RNA gene transcription in stably transfected cells. Consistent with other known bipartite promoter elements, the spacing between the GN3CCC and GACN5G elements was found to be critical for proper promoter function and correct transcription start point selection, as was the distance between the two elements and the wild-type transcription start point. The GACN5G element interacts specifically and in a double-stranded form with a protein(s) in Leishmania nuclear extracts. The degree of this protein DNA interaction in vitro correlated with SL RNA gene transcription efficiency in vivo, consistent with a role of the protein as a transcription factor. The core nucleotides GACN5G fit the consensus PSE promoter structure of pol II-transcribed snRNA genes in metazoa.
Animals↗
Cruciferous vegetables in relation to renal cell carcinoma.
Little is known about the possible role of diet in the development of renal cell carcinoma (RCC). A population-based case-control study was conducted in non-Asians of Los Angeles; it included 1,204 RCC patients and an equal number of neighborhood controls matched to the index cases by sex, date of birth (within 5 years) and ethnicity. Information on intake frequencies of food groups rich in vitamins A and C, various carotenoids and nitrosamines or their precursors was collected through in-person, structured interviews. After adjustment for non-dietary risk factors including level of education, obesity, history of hypertension, cigarette smoking and regular use of analgesics and amphetamines, there were strong inverse associations between cruciferous and dark green vegetable intakes and RCC risk (both p values for linear trend < 0.001). In terms of nutrients, there were significant inverse associations of RCC risk with consumption of a variety of carotenoids including alpha-carotene (p < 0.001), beta-carotene (p = 0.004), beta-cryptoxanthin (p = 0.01) and lutein (p = 0.005). However, after adjustment for these nutrients, we still observed a significant residual effect of cruciferous vegetables, suggesting that other substances present in these vegetables may be responsible, at least partially, for the observed reduction in risk of RCC. Dietary nitrosamines and their precursors were not related to RCC risk.
Adult↗
Nasopharyngeal carcinoma in Malaysian Chinese: salted fish and other dietary exposures.
We interviewed 282 histologically confirmed cases of nasopharyngeal carcinoma (NPC) in Chinese residents of Selangor and the Federal Territory, Malaysia, and an equal number of Chinese age-, sex-, and length-of-residence-matched controls sampled from the general population. Consumption of 55 dietary items during childhood, and 5 years pre-diagnosis of NPC, was analyzed by univariate and multivariate methods. Four salted preserved foods (fish, leafy vegetables, egg and root), fresh pork/beef organ meats and beer and liquor consumption exhibited strong positive associations, and 4 vegetable/fruit combinations strong negative associations with NPC. Factor analysis and multivariable modeling using estimated factor scores strongly supported separate effects on NPC of vegetables/fruits, salted preserved foods, pork/beef organ meats and beer/liquor consumption. Multivariable modeling associated NPC most clearly with high consumption of salted fish, salted eggs, pork/beef liver and beer and low consumption of Chinese flowering cabbage, oranges/tangerines and shrimp. A strong residual association of social class with NPC remained after adjustment for diet, which is consistent with a substantial role for non-dietary environmental factors.
Adult↗
Detection of ovarian cancer cells: comparison of a telomerase assay and cytologic examination.
BACKGROUND: Telomerase is an enzyme essential for the normal replication of chromosomes. Telomerase activity is absent in most somatic cells in adults, but it is usually expressed in cancer cells, including ovarian carcinoma cells. Our principal goal was to compare the sensitivity of a telomerase assay, i.e., the telomeric repeat amplification protocol (TRAP) assay, with that of cytologic examination in detecting cancer cells in the peritoneal cavity of patients with ovarian carcinoma. METHODS: TRAP assays and cytologic examinations were performed on peritoneal washings and ascitic fluids from 42 patients with active ovarian carcinoma. Control specimens included washings from 29 patients with benign ovarian diseases and ascitic fluids from 14 patients with liver failure. We also evaluated the stability of telomerase in ascitic fluids left unprocessed at room temperature as well as the ability of the TRAP assay to detect cancer cells in mixtures containing large numbers of normal cells. RESULTS: Specimens from 37 (88%) of the 42 patients with ovarian carcinoma tested positive for telomerase. Cytologic examination detected cancer cells in only 27 of the telomerase-positive specimens (i.e., in specimens from 64% of the 42 patients). This difference of 24% (95% confidence interval = 17%-30%) in sensitivity between the two tests was statistically significant (two-sided P = .002). Specimens from five of the patients with ovarian carcinoma were cytologically negative and telomerase negative. All 43 control specimens were cytologically negative, but the TRAP assay detected telomerase in two of them. Telomerase activity was detected in unprocessed samples left at room temperature for 5 days and in mixtures containing a small number of cancer cells and a 2000- to 10000-fold excess of normal cells. CONCLUSIONS: Assaying for telomerase is more sensitive than cytologic examination in detecting cancer cells in the peritoneal cavity of patients with ovarian carcinoma.
Ascitic Fluid↗
Hypertension, obesity and their medications in relation to renal cell carcinoma.
A population-based, case-control study was conducted in Los Angeles County, California, to investigate the inter-relationships of obesity, hypertension and medications in relation to renal cell carcinoma (RCC) risk. A total of 1204 RCC patients and an equal number of neighbourhood controls were included. Obesity was a strong risk factor for RCC. A fourfold increase in risk was observed for those with usual body mass index (kg m(-2)) of > or = 30 vs < 22. A history of hypertension was another strong, independent risk factor for RCC [odds ratio (OR) = 2.2; 95% confidence interval (CI) = 1.8, 2.6]. There was little evidence that use of diuretics was directly related to RCC development. Use of diuretics for reasons other than hypertension (primarily for weight control) was unrelated to risk among self-reported normotensive subjects (OR = 1.2; 95% CI = 0.7, 2.2). Among hypertensive subjects, heavy users of diuretics experienced similar risk as light users (OR = 0.9 among subjects with lifetime dose of > or = 137 g compared with those with lifetime dose of < 43 g). Similarly, normotensive subjects who took non-diuretic antihypertensives regularly showed no increased risk for RCC (OR = 1.1; 95% CI = 0.6-1.8), and intake among hypertensive subjects did not further increase their risk. Regular use of amphetamine-containing diet pills was associated with a twofold increase in RCC risk (95% CI = 1.4-2.8) and the risk increased with increasing dose of amphetamines. However, the fraction of cases possibly related to this exposure is small (population-attributable risk = 5%).
Adult↗
Report of invasive Rhodococcus equi infections in Taiwan, with an emphasis on the emergence of multidrug-resistant strains.
From November 1995 to October 1997, seven patients with invasive infections due to Rhodococcus equi were treated in Taiwan. Four patients had pulmonary lesions, and one each of the remaining three patients had a recurrent Port-A-Cath (Kabi-Pharmacia, North Ryde, New South Wales, Australia)-related bacteremia, a primary bacteremia, and a brain abscess. Three patients had underlying hematologic malignancies, and one each of the remaining four patients had diabetes mellitus, Waldenström's macroglobulinemia, long-term use of steroids, and AIDS. The 13 isolates of R. equi recovered from these patients were identified by using API Coryne System (bioMérieux, Marcy l'Etoile, France), VITEK GPI card (bioMérieux Vitek, Hazelwood, MO), supplemental biochemical tests, and cellular fatty acid chromatograms. Susceptibilities of these isolates to 16 antimicrobial agents, with use of the agar dilution method, varied; among them, amikacin and trimethoprim-sulfamethoxazole were the most active agents. Different random amplified polymorphic DNA (RAPD) patterns of isolates from different patients documented the lack of epidemiological relatedness of the causative organisms of these infections. This study confirms the emergence of multidrug-resistant R. equi infection in Taiwan and documents the relapsing or reactivating nature of this infection.
Actinomycetales Infections↗
Body weight and mortality: a prospective evaluation in a cohort of middle-aged men in Shanghai, China.
BACKGROUND: The relationship between relative body weight and mortality has been well studied in Western populations and remains controversial. Little is known about the weight-mortality association in less well fed people in developing countries. METHODS: A cohort of 18,244 Chinese men aged 45-64 years in Shanghai, China enrolled in a prospective study of diet and cancer during January 1986 through September 1989. At recruitment, height and usual body weight were collected through interview. An active, annual follow-up of the cohort was conducted for cancer and death. Proportional hazards regression method was used to examine the relation between body mass index (BMI, weight in kg/height in m2) and overall and cause-specific mortality. RESULTS: By 28 February 1995, 1198 deaths (498 from cancer, 422 from cardio- and cerebrovascular disease, and 278 from other causes) had been identified. We found a U-shaped relation between BMI and total mortality among lifelong non-smokers. Compared with non-smokers with BMI 21.0-<23.5, the relative risk (RR) for all cause mortality was 1.73 (95% confidence interval [CI]: 1.23-2.42) for men with BMI <18.5 and 1.48 (95% CI: 1.07-2.03) for men with BMI > or =26 after adjustment for age, level of education, and alcohol drinking. The elevated risk of death in men with BMI > or =26 was largely due to fatal cardio- and cerebro-vascular diseases. There was a nearly twofold excess risk of death from cardio- and cerebrovascular diseases among lifelong non-smokers with BMI > or =26 compared with non-smokers with BMI 21-<23.5 (95% CI: 1.17-3.22). On the other hand, the increased overall mortality risk in men with BMI <18.5 was primarily due to causes of an infectious origin. Exclusion of the first 4 years of follow-up data did not materially alter the BMI-mortality associations. CONCLUSION: Underweight and overweight both are associated with an increased risk of death in middle-aged Chinese men who never smoked cigarettes. The increased total mortality in overweight men is largely due to cardio- and cerebro-vascular diseases while the elevated risk of death in underweight men is attributed primarily to causes of an infectious nature.
Aged↗
Tuberculous empyema.
The clinical courses of 35 tuberculous empyema patients were investigated retrospectively from November 1990 through November 1995. Most patients had nonspecific symptoms and signs but with far-advanced pulmonary parenchymal lesions in their chest roentgenographs. The effusions showed neutrophilic leukocytosis with a 60% positive culture rate for Mycobacterium tuberculosis. Multidrug resistant strains were found in 7 out of 18 cultures. All patients received chemotherapy and eight of them underwent additional surgical management. Twenty-two (62.9%) patients had been treated successfully and one patient is still under treatment. The remaining 12 patients either died during treatment or defaulted; and four (11.4%) of them had died of tuberculosis. We conclude that the treatment outcome of tuberculous empyema is less satisfactory than that of pulmonary tuberculosis, however, modern multidrug chemotherapy with repeated drainage and opportune surgical interventions could be in prospect of successful treatment of tuberculous empyema.
Adolescent↗
Three small nucleolar RNAs identified from the spliced leader-associated RNA locus in kinetoplastid protozoans.
First characterized in Trypanosoma brucei, the spliced leader-associated (SLA) RNA gene locus has now been isolated from the kinetoplastids Leishmania tarentolae and Trypanosoma cruzi. In addition to the T. brucei SLA RNA, both L. tarentolae and T. cruzi SLA RNA repeat units also yield RNAs of 75 or 76 nucleotides (nt), 92 or 94 nt, and approximately 450 or approximately 350 nt, respectively, each with significant sequence identity to transcripts previously described from the T. brucei SLA RNA locus. Cell fractionation studies localize the three additional RNAs to the nucleolus; the presence of box C/D-like elements in two of the transcripts suggests that they are members of a class of small nucleolar RNAs (snoRNAs) that guide modification and cleavage of rRNAs. Candidate rRNA-snoRNA interactions can be found for one domain in each of the C/D element-containing RNAs. The putative target site for the 75/76-nt RNA is a highly conserved portion of the small subunit rRNA that contains 2'-O-ribose methylation at a conserved position (Gm1830) in L. tarentolae and in vertebrates. The 92/94-nt RNA has the potential to form base pairs near a conserved methylation site in the large subunit rRNA, which corresponds to position Gm4141 of small rRNA 2 in T. brucei. These data suggest that trypanosomatids do not obey the general 5-bp rule for snoRNA-mediated methylation.
Animals↗