Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “long noncoding RNA”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,153 records · Page 64Linked to original sources
PubMed2004

Molecular cloning and characterization of a novel sequence, vof-16, with enhanced expression in permanent ischemic rat brain.

We reported previously that chronic hypoperfusion induced by permanent occlusion of the bilateral common carotid arteries (2VO) in rats caused progressive cognitive deficits and neuronal damage in the hippocampus and the white matter. These changes are similar to those observed in human dementia. Reverse transcription-polymerase chain reaction (RT-PCR) differential display was carried out to identify mRNAs encoding the intrinsic factors involved in permanent ischemia from the 2VO rat brain. Over 20 clones which showed different expression levels in 2VO and sham-operated rats were isolated. One of these, named vof-16, was markedly enhanced the expression by 2VO. The whole sequence of vof-16 mRNA was 2098 nt. The distribution of vof-16 transcripts was examined by RT-PCR and in situ hybridization. The results revealed that vof-16 was abundant in the hippocampus, the tenia tecta, the piriform cortex and the area around the aorta. The expression levels of vof-16 in 2VO and sham-operated rat hippocampus were determined by a quantitative PCR method. The expression was abundant in the hippocampus of rats with cognitive impairment induced by 2VO. In contrast, the expression levels of vof-16 were lower in the 2VO rats with no impairment and in sham-operated rats. These results suggest that the expression levels of vof-16 may be related to the cognitive impairment induced by chronic ischemia after 2VO.

Animals↗
PubMed2026

Non-coding RNA 7SK drives tumor resistance by coupling local oncogenic activation with global transcriptional repression.

The conserved non-coding RNA 7SK is a well-established global transcriptional repressor, yet its context-specific functions in cancer and therapy resistance remain paradoxical. Here, we resolve this paradox by uncovering a dual-axis mechanism through which 7SK drives colorectal cancer (CRC) resistance. By integrating single-cell multi-omics with functional assays, we demonstrate that 7SK not only selectively activates the JUN transcriptional network to fuel tumor proliferation but also reduces global transcriptional entropy to stabilize an immunosuppressive microenvironment and promote immune escape. This "local activation-global suppression" paradigm is conserved across multiple cancer types, positioning 7SK as a potential pan-cancer therapeutic target. Our findings reveal 7SK as a dynamic modulator that balances oncogene-specific transcription with global transcriptional suppression across cancers, providing a new framework for understanding and targeting ncRNA-mediated resistance.

Humans↗
PubMed2025

Genetic analysis of IFNG-AS1 implicates opposite effects to Leishmania guyanensis-cutaneous leishmaniasis: rs4913269 confers protection while rs7134599 enhances susceptibility and correlates with high plasma IL-4 and IL-10 levels.

BACKGROUND: The long non-coding RNA interferon gamma antisense-1 (IFNGAS-1) is essential for Th1 lineage specific expression of IFNG. IFN-γ is a key component cytokine in host immune response against intracellular pathogens like Leishmania. We investigated the association of two genetic variants of IFNGAS-1, rs4913269 and rs7134599, with susceptibility or protection to Leishmania guyanensis- induced cutaneous leishmaniasis (Lg-CL). METHODS: A case-control study involving 1,714 individuals (855 Lg-CL and 859 healthy controls) was conducted in the state of Amazonas, Brazil. Genotyping of rs4913269 and rs7134599 were performed using direct nucleotide sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), respectively. Plasma cytokines concentrations (IL-10, IL-12p70, IL-4, IL-1β and TNF-α) were quantified using multiplex Luminex platform. Logistic regression, linkage disequilibrium (LD), and haplotype analyses were applied to assess genetic associations and cytokine correlations. RESULTS: Individuals with the rs4913269 G/G genotype had a 46% reduced risk of developing Lg-CL, (OR adjusted for age and sex [ORadj] = 0.54; 95% CI 0.39-0.75; Pvadj = 0.0001). Carriers of the rs7134599 A/A genotype had a 130% increased risk of progression to Lg- CL (ORadj = 2.3; 95% CI, 1.6-3.4; P = 0.0001). The rs7134599 A/G genotype also showed a 52% increased risk compared to GG genotype (ORadj = 1.52, 95%CI 1.22-1.89; Pvadj = 0.0002). The rs4913269 G/G genotype was associated with lower levels of IL-10 (P = 0.05) and IL-12p70 (P = 0.009) compared to the C/C genotype. Conversely, the rs7134599 AA genotypes were correlated with higher levels of TNF-α, IL-4, IL-10 and IL-1β in comparison to the GG genotype. LD revealed independent segregation of the variants. CONCLUSIONS: The IFNG-AS1 variants rs4913269 and rs7134599 exert opposing effects on Lg-CL risk and modulate key cytokines involved in disease pathogenesis. These findings underscore the regulatory role in immune responses and increase our understanding of the immunogenetic basis of CL and support the potential IFNG-AS1 as a biomarker for susceptibility.

Humans↗
PubMed2006

Regulated expression of two sets of paternally imprinted genes is necessary for mouse parthenogenetic development to term.

Mouse parthenogenetic embryos (PEs) are developmentally arrested until embryo day (E) 9.5 because of genomic imprinting. However, we have shown that embryos containing genomes from non-growing (ng) and fully grown (fg) oocytes, i.e. ng(wt)/fg(wt) PE (wt, wild type), developed to E13.5. Moreover, parthenogenetic development could be extended to term by further regulation of Igf2 and H19 expression using mice with deletion of the H19 transcription unit (H19Delta13) together with its differentially unit (DMR). To gain an insight into the extended development of the parthenotes to term, we have here investigated the expression levels of paternally imprinted genes in ng(H19Delta13)/fg(wt) PE throughout their development. In ng(H19Delta13)/fg(wt) Pes that died soon after recovery, the expression of Igf2 and H19 was restored to the appropriate levels except for low Igf2 expression in the liver after E15.5. Further, the paternally expressed Dlk1 and Dio3 were repressed, while the expression levels of the maternal Gtl2 and Mirg were twice those of the controls. However, the above-mentioned four genes showed almost normal expression in the surviving ng(H19Delta13)/fg(wt) PEs. The methylation analysis revealed that the intragenic DMR of the Dlk1-Gtl2 domain was hypermethylated in the ng(H19Delta13)/fg(wt) PEs that survived, but not in the PEs that died soon after recovery. The present study suggests that two sets of co-ordinately regulated but oppositely expressed genes, Igf2-H19 and Dlk1-Gtl2, act as a critical barrier to parthenogenetic development in order to render a paternal contribution obligatory for descendants in mammals.

Animals↗
PubMed2004

Cloning and sequencing of a cDNA encoding for a protein specifically expressed in human testis, ovary and placenta.

Reproductive cell/tissue-specific antigens are attractive candidates for the development of a contraceptive vaccine. Using the differential display technology, a human cDNA fragment of 322-bp, designated as T17, was identified showing specific expression in the human testis. The T17 cDNA fragment was used as a probe to screen the human testis cDNA-lambda gt10 library. After screening, one positive clone of approximately 1.1 kb having T17 nucleotide (nt) sequence was obtained. The 5' and 3' termini of this cDNA clone were extended by using 5' and 3' RACE procedures that yielded a full-length cDNA, designated as the TOP gene. The TOP cDNA is 1,480-bp long and has an ORF of 463 aa with the first ATG Met start codon at nucleotide (nt) 64 and the stop codon TGA at nt 1452. The translated protein has a calculated molecular mass of 49.3 kD with isoelectric point of 12.17. The deduced amino acid (aa) has one potential N-glycosylation site, and several phosphorylation and myristoylation sites. Hydropathy plot generated from the deduced aa sequence showed it to be a surface protein. Comprehensive computer search in the database did not reveal any homology to any existing sequences both at the nt and aa levels. The TOP cDNA was found to be completely localized on the human chromosome 16 at the nt position 507833-506354, with the TOP ORF at the nt position 507770-506354. Northern blot analysis using three human Northern blots, indicated the specific expression of TOP gene in the human testis, ovary and placenta. RT-PCR-Southern blot analysis also confirmed tissue-specific expression of the TOP gene. The TOP cDNA may help us to gain insight into transcriptional control of the differentially expressed reproductive tissue-specific genes. It may also find clinical applications in the development of a contraceptive vaccine, and specific diagnosis and treatment of infertility in humans.

Blotting, Northern↗
PubMed2026

Oxidative Stress Associated LncRNAs as Potential Biomarkers for Prognosis and Immune Responses in Lung Squamous Cell Carcinoma Patients.

Long-chain non-coding RNA (lncRNA) significantly influences lung squamous cell carcinoma's (LUSC) prognostic value and immune infiltration. This study aimed to demonstrate how oxidative stress-related lncRNAs impact lung squamous cell carcinoma (SCC). The Cancer Genome Atlas (TCGA) dataset gathered transcriptome information and related clinical data for LUSC. To build a prognostic model, 10 prognostic-related genes were identified using a series of bioinformatics analyses that compared the OS gene's aberrant expression in tumor and healthy tissues, as well as its association with malignancy. Subjects were stratified into high- and low-risk groups based on the median risk score derived from the 10-gene signature. While the mathematical risk model demonstrated limited independent predictive performance in the validation cohort (AUC ~ 0.5), functional and immunological evaluations revealed significant differences in the tumor microenvironment (TME) across risk strata. Specifically, high-risk patients exhibited distinct immune infiltration profiles and altered immunological scores relative to their low-risk counterparts. Therefore, rather than serving as a direct clinical prediction tool, this oxidative stress-related lncRNA signature provides valuable biological insights into the immune landscape of LUSC and highlights potential therapeutic targets for further mechanistic investigation.

Humans↗
PubMed2026

LINC01871-Mediated Sensitivity to Cyclin-Dependent Kinase 4/6 Inhibitors in Human Breast Cancer.

Breast cancer remains the most frequently diagnosed malignancy in women, and resistance to cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors limits long-term treatment efficacy. This study aimed to identify long non-coding RNAs (lncRNAs) associated with predicted sensitivity to CDK4/6 inhibitors and to investigate their biological functions in breast cancer. Transcriptomic data from The Cancer Genome Atlas (TCGA) and drug sensitivity data from the Genomics of Drug Sensitivity in Cancer 2 (GDSC2) database were integrated, and drug sensitivity was predicted using the oncoPredict algorithm. Candidate lncRNAs were identified through differential expression analysis, weighted gene co-expression network analysis, prognostic analysis, and machine learning. The biological functions of LINC01871 were subsequently evaluated using in vitro and in vivo experiments. Sixty-two lncRNAs associated with predicted sensitivity to ribociclib and palbociclib were identified, and six core lncRNAs were selected. LINC01871 showed the highest discriminatory performance for predicted drug sensitivity. Overexpression of LINC01871 was associated with increased sensitivity of breast cancer cells to ribociclib and palbociclib, inhibition of cell proliferation, promotion of apoptosis, and suppression of nuclear factor kappa B (NF-κB) signaling. Single-cell transcriptomic analysis demonstrated high LINC01871 expression in T cells and natural killer (NK) cells, while transcriptome-based immune infiltration analyses showed that high LINC01871 expression was associated with increased immune infiltration. These findings identify LINC01871 as a candidate biomarker of sensitivity to CDK4/6 inhibitors and demonstrate its tumor-suppressive effects in breast cancer. Further clinical and mechanistic studies are required to validate its predictive value and therapeutic relevance.

Humans↗
PubMed2026

LncRNA RP11-708J19.2 promotes colorectal cancer progression by binding to SIRT7 via regulating H3K18ac.

Colorectal cancer (CRC) is a prevalent malignancy with a complex genetic basis. Recent genome-wide association studies (GWAS) have identified a susceptibility locus at 3p21.31, however, the functional SNP(s) underlying the association between the 3p21.31 region and CRC remain to be elucidated. In this study, we identified rs2101247 as the potential functional SNP and further demonstrated that rs2101247 is significantly associated with the expression of the nearby long non-coding RNA (lncRNA) RP11-708J19.2 (ENSG00000271161.1). Functional experiments showed that RP11-708J19.2 is upregulated in CRC tumor tissues, and its knockdown reduces cell viability while promoting apoptosis in SW1116 and HCT116 cell lines. Mechanistically, RP11-708J19.2 interacts directly with the deacetylase SIRT7, modulating histone H3K18 acetylation (H3K18ac). Specifically, RP11-708J19.2 knockdown leads to a significant upregulation of H3K18ac levels, implicating a SIRT7-mediated epigenetic pathway in CRC progression. Our findings elucidate a novel functional SNP-lncRNA axis that contributes to CRC pathogenesis, providing potential biomarkers for early detection and therapeutic targets for intervention.

Humans↗
PubMed2006

Hashimoto's encephalopathy and motor neuron disease: a common autoimmune pathogenesis?

Hashimoto's encephalopathy is a rare complication of autoimmune thyroiditis not associated with thyroidal function decline. We report a 50-year-old man presenting with lower motor neuron symptoms evolving over 3 years and changes in behavior associated with attentive and cognitive impairment occurring in the last few months. Memory deficits, emotional instability, marked dysarthria, mild symmetric weakness of the lower extremities and fasciculations were the most striking clinical features. EEG was diffusely slow, cranial MRI revealed multiple subcortical white matter lesions, CSF protein was slightly elevated, electromyographic recordings showed acute and chronic denervation and extremely high TPO antibody titers were found in the serum. Hashimoto's encephalopathy and lower motor neuron disease were diagnosed. As repeated high-dose intravenous methylprednisolone administration followed by oral tapering improved both central nervous system and lower motor neuron symptoms, the question was raised whether there was a common autoimmune pathogenesis of both clinically distinct diseases.

Cerebral Cortex↗
PubMed1993

Primary structure, neural-specific expression, and dendritic location of human BC200 RNA.

Primate BC200 RNA is a 200-nucleotide-long, nontranslatable RNA that is prevalently expressed in the nervous system. We have determined the primary structure of human BC200 RNA, using cDNA cloning and PCR techniques. BC200 RNA can be subdivided into three structural domains. The 5' region is homologous to Alu repetitive elements that are found in high copy numbers in primate genomes. The central part of BC200 RNA is characterized by a high percentage of A-residues, with a few interspersed other nucleotides. The 3' sequence is unique to BC200 RNA and shows no apparent similarity with known human DNA sequences. Sequence similarity with rodent BC1 RNA is limited to several short elements, and BC1/BC200 sequence comparisons indicate that the two genes have evolved via separate phylogenetic routes. Probes directed against the 3' unique part of BC200 RNA detected a single band corresponding to approximately 200 nucleotides on RNA blots. This band was identified only with RNA isolated from human brain, not with RNA from non-neural organs such as lung or kidney. In situ hybridization to selected areas of the human nervous system showed that BC200 RNA is expressed by a subpopulation of neurons that is analogous to the BC1 RNA-expressing subset of neurons in the corresponding areas of the rat nervous system. Moreover, like rat BC1 RNA, human BC200 RNA was localized to dendrite-rich neuropil areas, for example, in the inner plexiform layer of the retina. These results indicate that BC1 RNA and BC200 RNA, although of different evolutionary pedigree, may play analogous functional roles, in rodents and primates, respectively, in somatodendritic domains of nerve cells.

Base Sequence↗
PubMed2025

Nascent and Mature RNA Profiling by Subcellular Fractionation in Human Cells.

Transcription and RNA decay determine steady-state RNA levels in cells available for translation and RNA-mediated regulatory functions. Both processes can be assessed by various techniques, for majority, based on RNA labelling or chromatin immunoprecipitation, but require a high level of expertise. Here, we describe a cost-effective, fast, and simple protocol that enables the profiling of nascent and mature RNA in the cytoplasm, nucleoplasm, and chromatin through subcellular fractionation. The workflow can include α-amanitin inhibition of RNA Polymerase II to assess nascent RNAs as a proxy of transcriptional activity, or it can be used without this treatment to investigate distribution of partially processed or mature transcripts across distinct subcellular compartments. It is applicable for studying any of RNA biotypes, including small and long noncoding RNAs, mRNAs, and their splice variants, on both transcript-specific and transcriptome-wide scales. Nascent or mature RNAs isolated from each fraction can be further analyzed by any technique of choice (northern blot, reverse transcription, RNA sequencing).

Humans↗
PubMed1990

Mutational analysis of the pseudoknot region in the 3' noncoding region of tobacco mosaic virus RNA.

The approximately 200-nucleotide-long 3'-terminal noncoding region of tobacco mosaic virus (TMV) RNA contains a tRNA-like structure and, in its immediate upstream region, three consecutive pseudoknots, each of which is composed of two double-helical segments. To elucidate the biological functions of the pseudoknot region, we constructed several deletion mutant TMV-L (a tomato strain) RNAs by using an in vitro transcription system and tested their ability to multiply in both tobacco plants and protoplasts. When deletions were introduced just downstream of the termination codon of the coat protein gene in the 5'-to-3' direction progressively, five of six double-helical segments were dispensable for viral multiplication, indicating that the pseudoknot structures are not essential for multiplication. However, extension of the deletion into the central pseudoknot region resulted in reduction in viral multiplication, accompanied by loss of development of mosaic symptoms on systemic tobacco plants. Cessation of multiplication was observed when the sequence involved in formation of double-helical segment I just upstream of the tRNA-like structure was deleted irrespective of the start point and extent of deletion. Point mutations that destabilized double-helical segment I resulted in a loss or great reduction of viral multiplication, whereas the double mutants in which the double helix was restored by additional compensating base substitutions restored multiplication to nearly the wild-type level. Thus, double-helical segment I just upstream of the tRNA-like structure is a structural feature essential for viral multiplication.

Base Sequence↗
PubMed1991

Dendritic location of neural BC1 RNA.

In nerve cells, a specialized protein synthetic machinery is thought to operate in local compartments of dendrites, in particular beneath synaptic junctions, and thereby to facilitate swift adjustments of the postsynaptic protein repertoire in situ. This notion has been supported by the identification of polyribosomes and selected mRNAs in those compartments. In this study, we report the discovery of a specific RNA polymerase III transcript in dendrites. This RNA, a noncoding, 152-nucleotide-long, single-gene transcript known as BC1 RNA, is expressed almost exclusively in the nervous system. In adult rats as well as in immature rats in late developmental stages, BC1 RNA has been located in the dendrites and somata of a subset of neurons in the central and peripheral nervous system. The colocalization of BC1 RNA with dendritic mRNAs and polyribosomes may indicate a role--possibly within the functional unit of a high molecular mass ribonucleoprotein particle--in specific pre- or posttranslational processes in postsynaptic compartments of neurons.

Animals↗
PubMed2025

RNA G-quadruplexes emerge from a compacted coil-like ensemble via multiple pathways.

RNA G-quadruplexes (rG4s) are emerging as vital structural elements involved in processes like gene regulation, translation, and genome stability. Found in untranslated regions of messenger RNAs (mRNAs), they influence translation efficiency and mRNA localization. Additionally, rG4s of long noncoding RNAs and telomeric RNA play roles in RNA processing and cellular aging. Despite their significance, the atomic-level folding mechanisms of rG4s remain poorly understood due to their complexity. We studied the folding of the r(GGGA)3GGG and r(GGGUUA)3GGG (TERRA) sequences into parallel-stranded rG4 using all-atom enhanced-sampling molecular dynamics simulations, applying well-tempered metadynamics coupled with solute tempering. The obtained folding pathways suggest that RNA initially adopts a compacted coil-like ensemble characterized by dynamic guanine stacking and pairing. The three-quartet rG4 gradually forms from this compacted coil ensemble via diverse routes involving strand rearrangements and guanine incorporations. While the folding mechanism is multipathway, various two-quartet rG4 structures appear to be a common transitory ensemble along most routes. Thus, the process seems more complex than previously predicted, as G-hairpins or G-triplexes do not act as distinct intermediates, even though some are occasionally sampled. We also discuss the challenges of applying enhanced sampling methodologies to such a multidimensional free-energy surface and address the force-field limitations.

G-Quadruplexes↗
PubMed1982

Complete nucleotide sequences of the coat protein messenger RNAs of brome mosaic virus and cowpea chlorotic mottle virus.

The nucleotide sequences of the subgenomic coat protein messengers (RNA4's) of two related bromoviruses, brome mosaic virus (BMV) and cowpea chlorotic mottle virus (CCMV), have been determined by direct RNA and CDNA sequencing without cloning. BMV RNA4 is 876 b long including a 5' noncoding region of nine nucleotides and a 3' noncoding region of 300 nucleotides. CCMV RNA 4 is 824 b long, including a 5' noncoding region of 10 nucleotides and a 3' noncoding region of 244 nucleotides. The encoded coat proteins are similar in length (188 amino acids for BMV and 189 amino acids for CCMV) and display about 70% homology in their amino acid sequences. Length difference between the two RNAs is due mostly to a single deletion, in CCMV with respect to BMV, of about 57 b immediately following the coding region. Allowing for this deletion the RNAs are indicate that mutations leading to divergence were constrained in the coding region primarily by the requirement of maintaining a favorable coat protein structure and in the 3' noncoding region primarily by the requirement of maintaining a favorable RNA spatial configuration.

Amino Acid Sequence↗
PubMed1993

The secondary structure of the 5'-noncoding region of beet necrotic yellow vein virus RNA 3: evidence for a role in viral RNA replication.

Secondary structure-sensitive chemical and enzymatic probes have been used to produce a model for the folding of the first 312 residues of the long 5'-noncoding region of beet necrotic yellow vein virus RNA 3. The structure consists of two major domains, one of which includes long distance base-pairing interactions between two short sequence elements (Box I and Box II) situated between positions 237 and 292 and complementary elements (Box I' and II') near the 5'-terminus. Previous studies have shown that base pairing between these sequence elements (in either the plus-strand or minus-strand RNA) is important for RNA 3 accumulation during infection. RNA 3 transcripts were produced containing mutations which preferentially disrupted Box II-II' base pairing in either the plus- or minus-strand. In infection experiments, transcripts with mutations which disrupted the Box II-II' interaction in the plus-strand structure replicated less efficiently than mutants in which the Box II-II' interaction was disrupted in the minus-strand. These findings indicate that the complex 5'-proximal plus-strand structure to which the Box II-II' interaction contributes comprises at least part of the promoter for plus-strand RNA synthesis.

Base Sequence↗
PubMed1993

Identification of the hepatitis A virus internal ribosome entry site: in vivo and in vitro analysis of bicistronic RNAs containing the HAV 5' noncoding region.

Hepatitis A virus (HAV), a RNA virus of positive polarity, contains a long 5' noncoding region (5'NCR) that lacks the characteristic m7GpppN cap group of most eukaryotic messages. By creating bicistronic constructs that contain the bacterial chloramphenicol acetyltransferase gene followed by the HAV 5'NCR and the luciferase gene we have demonstrated by assaying in vitro and in vivo that ribosome entry for translation initiation occurs via binding to sequences within the HAV 5'NCR. Using mutations created within this region we have identified that the HAV internal ribosome entry site (IRES) is located downstream of nucleotide 45 and including sequences up to nucleotide 734 of the HAV 5'NCR. Translation of a number of mutant constructs both in vitro in a rabbit reticulocyte lysate and in vivo by transfection of the cDNAs into BS-C-1 cells in the presence of the recombinant vaccinia virus, vTF7-3, gave similar results. However, a 4-nucleotide insertion at base 628 showed an increased activity over wild-type when transfected into BS-C-1 cells that was not seen in vitro. This increase in activity correlated with an increase in luciferase gene product as assayed by immunoprecipitations of [35S]methionine radiolabeled cells. Comparison of mono- and bicistronic RNAs that were synthesized with or without a m7GpppG cap group showed a competition for ribosome binding when translated in a rabbit reticulocyte lysate system. The presence of the cap group on the RNA 5'terminus of the RNA led to a greater ability of this RNA to translate than the RNA containing the HAV IRES.

Animals↗
PubMed1982

Nucleotide sequence surrounding multiple polyadenylation sites in the mouse dihydrofolate reductase gene.

We have previously reported the presence of four dihydrofolate reductase messenger RNAs differing in the length of 3' untranslated regions in murine cells (Setzer, D. R., McGrogan, M., Nunberg, J. H., and Schimke, R. T. (1980) Cell 22, 361-370). We have now mapped the 3' ends of these RNAs more precisely and have demonstrated colinearity between their shared sequences. Analysis of three larger dihydrofolate reductase RNAs has shown that these RNA species contain very long 3' noncoding regions, bringing the total number of dihydrofolate reductase RNAs to seven, ranging in length from 750 to 5600 nucleotides. We have determined the nucleotide sequence at and surrounding the polyadenylation sites of the four smaller RNAs. We find no striking structures in this sequence that might constitute multiple polyadenylation signals, but conclude that the putative polyadenylation signal AAUAAA is not required for polyadenylation of at least three of the four dihydrofolate reductase messengers.

Animals↗