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At least 307 records · Page 17Linked to original sources
PubMed1999

Phosphorylation of rabies virus nucleoprotein regulates viral RNA transcription and replication by modulating leader RNA encapsidation.

One of the major structural differences between rabies virus and vesicular stomatitis virus (VSV) is that the nucleoprotein (N) is the major phosphoprotein and the nominal phosphoprotein (P) is less phosphorylated in rabies virus, whereas P is the major phosphoprotein and N is not phosphorylated in VSV. We investigated the function of phosphorylation of rabies virus N after dephosphorylation of N with alkaline phosphatase or after changing the phosphorylated serine at position 389 to alanine by site-directed mutagenesis. The unphosphorylated N, in comparison to the phosphorylated N, was studied for its abilities to encapsidate rabies virus leader RNA and to support transcription and replication of a rabies virus minigenome. We found that unphosphorylated N binds more strongly to leader RNA than the phosphorylated N; however, the rates of transcription and replication of the rabies virus minigenome were significantly lower with the unphosphorylated N than with the phosphorylated N. This indicates that the phosphorylation of rabies virus N plays an important role in the regulation of rabies virus transcription and replication, probably via modulation of leader RNA encapsidation.

5' Untranslated Regions↗
PubMed2003

Regulation by RNA.

In recent years, noncoding RNAs (ncRNAs) have been shown to constitute key elements implicated in a number of regulatory mechanisms in the cell. They are present in bacteria and eukaryotes. The ncRNAs are involved in regulation of expression at both transcriptional and posttranscriptional levels, by mediating chromatin modifications, modulating transcription factor activity, and influencing mRNA stability, processing, and translation. Noncoding RNAs play a key role in genetic imprinting, dosage compensation of X-chromosome-linked genes, and many processes of differentiation and development.

Animals↗
PubMed1996

Inverse association of cell adhesion regulator messenger RNA expression with metastasis in human colorectal cancer.

Alterations in several classes of adhesion molecules have been implicated in the progression of colorectal cancer. Cell adhesion regulator (CAR) has been identified as a regulator molecule of integrin-dependent cell adhesion. We have explored a possible involvement of the CAR gene in colorectal cancer. Reverse transcription-PCR revealed that CAR expression was detected in normal colonic cells, whereas it was decreased or undetectable in 6 of 13 (46.2%) human colon cancer cell lines. To further study the biological significance of CAR expression in colon cancer cells, a CAR expression vector was introduced into HT-29 cells, in which CAR is not expressed. Adhesion of HT-29 cells to extracellular matrix components was up-regulated by the introduction of CAR. In spite of similar growth properties with the controls, CAR-transfected HT-29 cells showed a significantly reduced spontaneous metastatic potential in nude mice. To determine whether these experimental results are of relevance with respect to actual human tumors, we investigated CAR expression in 30 surgical specimen pairs of human colorectal cancer and adjacent noncancerous tissue using semiquantitative reverse transcription-PCR. In 14 of 30 cases (46.7%), CAR expression in cancer was less than one-tenth of that in matched noncancerous tissue. The tumor:normal ratio of CAR expression was significantly lower in patients with lymph node metastasis than in those without it (P < 0.01) and in patients with distant metastasis than in those without it (P < 0.05). CAR expression was significantly lower in more advanced Dukes' stage tumors (P < 0.05). Our results suggest that down-regulation of CAR expression may play an important role in the progression and metastasis of colorectal cancer.

ATPases Associated with Diverse Cellular Activitie↗
PubMed2002

Differential regulation of RNA levels of gibberellin dioxygenases by photoperiod in spinach.

Previous work with spinach (Spinacia oleracea) has shown that the level of gibberellin (GA) 20-oxidase is strongly up-regulated by long days (LD). In the present work, the effect of photoperiod on expression of other GA dioxygenases was investigated and compared with that of GA 20-oxidase. Two GA 2-oxidases and one GA 3-oxidase were isolated from spinach by reverse transcription-polymerase chain reaction with degenerate primers and by 5'- and 3'-rapid amplification of cDNA ends. As determined by high-performance liquid chromatography with on-line radioactivity detection, the SoGA3ox1 gene product catalyzed 3beta-hydroxylation of GA(9) to GA(4) and GA(20) to GA(1). The SoGA2ox1 and the SoGA2ox2 gene products catalyzed 2beta-hydroxylation of GA(9) to GA(51) and GA(20) to GA(29). The product of GA(20) metabolism by SoGA3ox1 was identified as GA(1) by gas chromatography-mass spectrometry, whereas the products of GA(1) and GA(20) metabolism by SoGA2ox1 and SoGA2ox2 were identified as GA(8) and GA(29), respectively. SoGA2ox1 also metabolized GA(53) to GA(97). The levels of SoGA20ox1 transcripts were greatly increased in all organs tested in LD conditions, but the levels of SoGA3ox1 transcripts were only slightly increased in blades and petioles. A decrease in the levels of the SoGA2ox1 transcripts in young leaves and tips in LD conditions is opposite to the expression pattern of the SoGA20ox1. Expression of SoGA20ox1 in petioles and young leaves was strongly up-regulated by a supplementary 16 h of light, but the levels of SoGA3ox1 and SoGA2ox1 transcripts did not change. It is concluded that regulation and maintenance of GA(1) concentration in spinach are primarily attributable to changes in expression of SoGA20ox1.

Amino Acid Sequence↗
PubMed1991

Tissue- and development-specific alternative RNA splicing regulates expression of multiple isoforms of erythroid membrane protein 4.1.

Protein 4.1, a multifunctional structural protein originally described as an 80-kDa component of the erythroid membrane skeleton, exhibits tissue- and development-specific heterogeneity in molecular weight, subcellular localization, and primary amino acid sequence. Earlier reports suggested that some of this impressive heterogeneity is generated by alternative RNA splicing (Conboy, J. G., Chan, J., Mohandas, N., and Kan, Y. W. (1988) Proc. Natl. Acad. Sci. U. S. A. 85, 9062-9065; Tang, T. K., Leto, T., Marchesi, V. T., and Benz, E. J. (1990) J. Cell Biol. 110, 617-624). We have now completed a systematic analysis of 4.1 mRNA isoforms expressed in erythroid cells, and have generated an "alternative splicing map" which summarizes diagrammatically a multitude of polypeptide isoforms potentially generated by combinatorial splicing of nine alternative exons. Complex 5' splicing events yield mRNA isoforms that may initiate translation at different sites and thus generate elongated or truncated NH2 termini; elongated approximately 135-kDa and prototypical approximately 80-kDa species were detected in both erythrocytes and T-lymphocytes, but in very different ratios. Among the functional domains of 4.1 responsible for interaction with other membrane skeletal elements, four variants of the 10-kDa spectrin-actin-binding region and four variants of the putative 30-kDa glycophorin-binding region are predicted. Developmentally controlled alternative RNA splicing in the spectrin-actin-binding region may help regulate remodeling of membrane architecture and mechanical properties that occur during erythropoiesis.

Amino Acid Sequence↗
PubMed1984

Removal of a terminator structure by RNA processing regulates int gene expression.

The int gene of phage lambda encodes a protein involved in site-specific recombination. Its expression is regulated differentially during successive phases of the lambda infective cycle. The gene is transcribed early after infection from one promoter, pL, and later from a second promoter pI. Each transcription event requires different positive activation factors, lambda N and cII proteins, respectively. Transcription from the pI promoter, located adjacent to int, passes through int and terminates 277 nucleotides beyond int at tI. Polymerases initiating at pL transcribe through tI and into the b segment of lambda DNA. The read-through pL transcript is sensitive to cleavage by the endonuclease, RNase III, both in vivo and in vitro. Two specific cuts are made by RNase III in a double-stranded structure about 260 nucleotides beyond int in the location of the tI terminator. Functionally, the processed pL transcript is unable to synthesize the int gene product, whereas the terminated and unprocessed pI transcript expresses int. Interestingly, unprocessed pL transcripts made in hosts defective in RNase III (rnc-) can express int. Thus a correlation exists between processing and negative control of int expression. The place where processing occurs, some 260 nucleotides beyond int, is called sib, and the control of int expression from this site is called retroregulation. Retroregulation by sib is not restricted just to the int gene; we show that if the sib site is cloned beyond a bacterial gene, the gene is controlled by sib and RNase III. Specific models are discussed with respect to control of gene expression by RNase III from a site beyond the controlled gene.

Bacteriophage lambda↗
PubMed2000

Site-specific modification and RNA crosslinking of the RNA-binding domain of PKR.

RNA-dependent protein kinase (PKR) is an interferon-induced, RNA-activated enzyme that phosphorylates and inhibits the function of the translation initiation factor eIF-2. PKR is activated in vitro by binding RNA molecules with extensive duplex structure. To further define the nature of the RNA regulation of PKR, we have prepared and characterized site-specifically modified proteins consisting of the PKR 20 kDa RNA-binding domain (RBD). Here we show that the two cysteines found naturally in this domain can be altered by site-directed mutagenesis without loss of RNA binding affinity or the RNA-regulated kinase activity. Introduction of cysteine residues at other sites in the PKR RBD allows for site-specific modification with thiol-selective reagents. PKR RBD mutants reacted selectively with a maleimide to introduce a photoactivatable cross-linking aryl azide at three different positions in the protein. RNA crosslinking efficiency was found to be dependent on the amino acid modified, suggesting differences in access to the RNA from these positions in the protein. One of the amino acid modifications that led to crosslinking of the RNA is located at a residue known to be an autophosphorylation site, suggesting that autophosphorylation at this site could influence the RNA binding properties of PKR. The PKR RBD conjugates described here and other similar reagents prepared via these methods are applicable to future studies of PKR-RNA complexes using techniques such as photocrosslinking, fluorescence resonance energy transfer and affinity cleaving.

Base Sequence↗
PubMed2000

Naturally occurring dicistronic cricket paralysis virus RNA is regulated by two internal ribosome entry sites.

Cricket paralysis virus is a member of a group of insect picorna-like viruses. Cloning and sequencing of the single plus-strand RNA genome revealed the presence of two nonoverlapping open reading frames, ORF1 and ORF2, that encode the nonstructural and structural proteins, respectively. We show that each ORF is preceded by one internal ribosome entry site (IRES). The intergenic IRES is located 6,024 nucleotides from the 5' end of the viral RNA and is more active than the IRES located at the 5' end of the RNA, providing a mechanistic explanation for the increased abundance of structural proteins relative to nonstructural proteins in infected cells. Mutational analysis of this intergenic-region IRES revealed that ORF2 begins with a noncognate CCU triplet. Complementarity of this CCU triplet with sequences in the IRES is important for IRES function, pointing to an involvement of RNA-RNA interactions in translation initiation. Thus, the cricket paralysis virus genome is an example of a naturally occurring, functionally dicistronic eukaryotic mRNA whose translation is controlled by two IRES elements located at the 5' end and in the middle of the mRNA. This finding argues that eukaryotic mRNAs can express multiple proteins not only by polyprotein processing, reinitiation and frameshifting but also by using multiple IRES elements.

Animals↗
PubMed1990

Secondary structure of the human T-cell leukemia virus type 1 rex-responsive element is essential for rex regulation of RNA processing and transport of unspliced RNAs.

Rex protein of human T-cell leukemia virus type 1 (HTLV-1) induces cytoplasmic expression of unspliced gag/pol mRNA and singly spliced env mRNA and thus is essential for replication of the virus. This regulation requires a cis-acting rex-responsive element (RXE), located in the 3' region of the viral RNA. By external deletion, we have identified RXE composed of 205 nucleotides. The secondary structure of RXE was confirmed by studies on its susceptibility to nuclease digestions to consist of four stem-loops and a long stretch of stem structure. Substitution and deletion mutations revealed that two regions of the stem-loops and their secondary structures are essential for rex regulation. Similar secondary structures were found in the corresponding regions of HTLV-2, bovine leukemia virus and human immunodeficiency virus. Furthermore, a sequence of 11 nucleotides in the RXE was found to be conserved in the secondary structures of HTLV-1, HTLV-2, and bovine leukemia virus. These observations suggest that the secondary structure as well as the conserved sequence may be important in expression of unspliced RNA even with diverged sequences as observed in these viruses.

Base Sequence↗
PubMed2001

Phosphorylation down-regulates the RNA binding function of the coat protein of potato virus A.

Plant viruses encode movement proteins (MPs) to facilitate transport of their genomes from infected into neighboring healthy cells through plasmodesmata. Growing evidence suggests that specific phosphorylation events can regulate MP functions. The coat protein (CP) of potato virus A (PVA; genus Potyvirus) is a multifunctional protein involved both in virion assembly and virus movement. Labeling of PVA-infected tobacco leaves with [(33)P]orthophosphate demonstrated that PVA CP is phosphorylated in vivo. Competition assays established that PVA CP and the well characterized 30-kDa MP of tobacco mosaic virus (genus Tobamovirus) are phosphorylated in vitro by the same Ser/Thr kinase activity from tobacco leaves. This activity exhibits a strong preference for Mn(2+) over Mg(2+), can be inhibited by micromolar concentrations of Zn(2+) and Cd(2+), and is not Ca(2+)-dependent. Tryptic phosphopeptide mapping revealed that PVA CP was phosphorylated by this protein kinase activity on multiple sites. In contrast, PVA CP was not phosphorylated when packaged into virions, suggesting that the phosphorylation sites are located within the RNA binding domain and not exposed on the surface of the virion. Furthermore, two independent experimental approaches demonstrated that the RNA binding function of PVA CP is strongly inhibited by phosphorylation. From these findings, we suggest that protein phosphorylation represents a possible mechanism regulating formation and/or stability of viral ribonucleoproteins in planta.

Binding, Competitive↗
PubMed2006

Alternative RNA splicing regulation in the testis.

Alternative splicing regulation has been shown to be critically important for several developmental pathways. It is particularly prevalent in the testis, which is the site of an extensive adult developmental programme. Alternative splicing is controlled by a splicing code, in which transcripts respond to subtle cell type-specific variations in positive and negative trans-acting RNA-binding proteins according to their unique set of binding sites for these proteins. Because of their unique combinations of cis-acting sequence elements, specific transcripts are able to respond individually to this code. In this review, we discuss how this code may be deciphered in germ cells to mediate a splicing response.

Adult↗
PubMed2005

RNAi and RNA-based regulation of immune system function.

Gene regulation by short RNAs is a ubiquitous and important mode of control. MicroRNAs are short, single-strand RNAs that bind with partial complementarity to the 3' untranslated region of several genes to silence their expression. This expanding class of endogenous short RNAs are evolutionarily conserved and participate in control of development and cell-specific gene function. Several of these microRNAs have been cloned uniquely from mammalian lymphocytes suggesting specialized roles in lymphocyte development and function. In addition, several genes linked to RNAi in lower eukaryotes have mammalian homologs with specialized roles in adaptive immunity. For example, in worms, the nonsense-mediated decay (NMD) and RNAi pathways appear to be intricately linked. NMD plays a key role in regulating antigen-receptor expression in lymphocytes and there are mammalian homologs for factors identified in worms that appear to be common in both RNAi and NMD pathways. On the other hand, RNA editing and RNAi have an inverse relationship and RNA editing has an important role in viral immunity. These observations indicate unique roles for dsRNAs in the mammalian immune system.

APOBEC-1 Deaminase↗
PubMed2004

Hrb27C, Sqd and Otu cooperatively regulate gurken RNA localization and mediate nurse cell chromosome dispersion in Drosophila oogenesis.

Heterogeneous nuclear ribonucleoproteins, hnRNPs, are RNA-binding proteins that play crucial roles in controlling gene expression. In Drosophila oogenesis, the hnRNP Squid (Sqd) functions in the localization and translational regulation of gurken (grk) mRNA. We show that Sqd interacts with Hrb27C, an hnRNP previously implicated in splicing. Like sqd, hrb27C mutants lay eggs with dorsoventral defects and Hrb27C can directly bind to grk RNA. Our data demonstrate a novel role for Hrb27C in promoting grk localization. We also observe a direct physical interaction between Hrb27C and Ovarian tumor (Otu), a cytoplasmic protein implicated in RNA localization. We find that some otu alleles produce dorsalized eggs and it appears that Otu cooperates with Hrb27C and Sqd in the oocyte to mediate proper grk localization. All three mutants share another phenotype, persistent polytene nurse cell chromosomes. Our analyses support dual cooperative roles for Sqd, Hrb27C and Otu during Drosophila oogenesis.

Animals↗
PubMed2002

Control of developmental timing by small temporal RNAs: a paradigm for RNA-mediated regulation of gene expression.

Heterochronic genes control the timing of developmental programs. In C. elegans, two key genes in the heterochronic pathway, lin-4 and let-7, encode small temporally expressed RNAs (stRNAs) that are not translated into protein. These stRNAs exert negative post-transcriptional regulation by binding to complementary sequences in the 3' untranslated regions of their target genes. stRNAs are transcribed as longer precursor RNAs that are processed by the RNase Dicer/DCR-1 and members of the RDE-1/AGO1 family of proteins, which are better known for their roles in RNA interference (RNAi). However, stRNA function appears unrelated to RNAi. Both sequence and temporal regulation of let-7 stRNA is conserved in other animal species suggesting that this is an evolutionarily ancient gene. Indeed, C. elegans, Drosophila and humans encode at least 86 other RNAs with similar structural features to lin-4 and let-7. We postulate that other small non-coding RNAs may function as stRNAs to control temporal identity during development in C. elegans and other organisms.

3' Untranslated Regions↗
PubMed1973

Temperature-sensitive relaxed Phenotype in a stringent strain of Escherichia coli.

A temperature-sensitive elongation factor G (EF-G) mutation carried by a rel strain of Escherichia coli was transferred to a rel(+) strain. The recombinant (AA-10) was found to be temperature-sensitive "relaxed" for ribonucleic acid (RNA) regulation. However, when a temperature-sensitive EF-G is present in a strain temperature-sensitive for valyl-transfer RNA (tRNA) synthetase, this new strain (AA-16) is no longer temperature-sensitive "relaxed" for RNA regulation. In strain AA-10, all tRNAs remain fully charged, and in AA-16 tRNA(val) becomes completely discharged at the nonpermissive growth temperature. Also, synthesis of ppGpp is not observed in strain AA-10 at 42 C but is observed at 42 C in strain AA-16.

Amino Acyl-tRNA Synthetases↗