RNA
1355-8382
1469-9001
Mỹ
Cơ quản chủ quản: COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT , Cold Spring Harbor Laboratory Press
Lĩnh vực:
Molecular Biology
Phân tích ảnh hưởng
Thông tin về tạp chí
RNA is a monthly journal which provides rapid publication of significant original research in all areas of RNA structure and function in eukaryotic, prokaryotic, and viral systems. It covers a broad range of subjects in RNA research, including: structural analysis by biochemical or biophysical means; mRNA structure, function and biogenesis; alternative processing: cis-acting elements and trans-acting factors; ribosome structure and function; translational control; RNA catalysis; tRNA structure, function, biogenesis and identity; RNA editing; rRNA structure, function and biogenesis; RNA transport and localization; regulatory RNAs; large and small RNP structure, function and biogenesis; viral RNA metabolism; RNA stability and turnover; in vitro evolution; and RNA chemistry.
Các bài báo tiêu biểu
Ubiquitin binding by a variant Jab1/MPN domain in the essential pre-mRNA splicing factor Prp8p The U1, U2, U4/U6, and U5 small nuclear ribonucleoproteins (snRNPs) are components of the spliceosome, which catalyzes pre-mRNA splicing. One of the largest and the most highly conserved proteins in the spliceosome is Prp8p, a component of the U5 snRNP. Despite its size and conservation, very few motifs have been identified that suggest specific biochemical functions. A variant of the Jab1/MPN domain found in a class of deubiquitinating enzymes is present near the C terminus of Prp8p. Ubiquitination regulates a broad range of cellular pathways, and its functions generally require ubiquitin recognition by one or more ubiquitin-binding domains (UBDs). No precise role for ubiquitin has been defined in the pre-mRNA splicing pathway, and no known UBDs have been found within splicing proteins. Here we show that a Prp8p fragment containing the Jab1/MPN domain binds directly to ubiquitin with an affinity comparable to other known UBDs. Several mutations within this domain that compromise splicing also reduce interaction of the fragment with ubiquitin-Sepharose. Our results define a new UBD and suggest functional links between ubiquitin and the pre-mRNA splicing machinery.
Tập 12 Số 2 - Trang 292-302 - 2006
Expression of the essential mRNA export factor Yra1p is autoregulated by a splicing-dependent mechanism
Tập 8 Số 8 - Trang 969-980 - 2002
Autoregulation of the mRNA export factor Yra1p requires inefficient splicing of its pre-mRNA Yra1p is an essential RNA-binding protein that couples transcription to export. The YRA1 gene is one of only ∼5% of genes that undergo splicing in budding yeast, and its intron is unusual in several respects, including its large size and anomalous branchpoint sequence. We showed previously that the intron is required for autogenous regulation of Yra1p levels, which cause a dominant negative growth phenotype when elevated. The mechanism of this regulation, however, remains unknown. Here we demonstrate that growth is inversely correlated with splicing efficiency. Substitution of a canonical branchpoint moderately improves splicing but compromises autoregulation. Shortening the intron from 766 to ∼350 nt significantly improves splicing but abolishes autoregulation. Notably, proper regulation can be restored by insertion of unrelated sequences into the shortened intron. In that the current paradigm for regulated splicing involves the binding of protein factors to specific elements in the pre-mRNA, the regulation of YRA1 expression appears to occur by a novel mechanism. We propose that appropriate levels of Yra1p are maintained by inefficient cotranscriptional splicing.
Tập 12 Số 6 - Trang 994-1006 - 2006
Genome-wide bioinformatic and molecular analysis of introns in Saccharomyces cerevisiae
Tập 5 Số 2 - Trang 221-234 - 1999
Molecular architecture of a miRNA-regulated 3′ UTR Animal genomes contain hundreds of microRNAs (miRNAs), small regulatory RNAs that control gene expression by binding to complementary sites in target mRNAs. Some rules that govern miRNA/target interaction have been elucidated but their general applicability awaits further experimentation on a case-by-case basis. We use here an assay system in transgenic nematodes to analyze the interaction of the Caenorhabditis elegans lsy-6 miRNA with 3′ UTR sequences. In contrast to many previously described assay systems used to analyze miRNA/target interactions, our assay system operates within the cellular context in which lsy-6 normally functions, a single neuron in the nervous system of C. elegans . Through extensive mutational analysis, we define features in the known and experimentally validated target of lsy-6 , the 3′ UTR of the cog-1 homeobox gene, that are required for a functional miRNA/target interaction. We describe that both in the context of the cog-1 3′ UTR and in the context of heterologous 3′ UTRs, one or more seed matches are not a reliable predictor for a functional miRNA/target interaction. We rather find that two nonsequence specific contextual features beyond miRNA target sites are critical determinants of miRNA-mediated 3′ UTR regulation. The contextual features reside 3′ of lsy-6 binding sites in the 3′ UTR and act in a combinatorial manner; mutation of each results in limited defects in 3′ UTR regulation, but a combinatorial deletion results in complete loss of 3′ UTR regulation. Together with two lsy-6 sites, these two contextual features are capable of imparting regulation on a heterologous 3′ UTR. Moreover, the contextual features need to be present in a specific configuration relative to miRNA binding sites and could either represent protein binding sites or provide an appropriate structural context. We conclude that a given target site resides in a 3′ UTR context that evolved beyond target site complementarity to support regulation by a specific miRNA. The large number of 3′ UTRs that we analyzed in this study will also be useful to computational biologists in designing the next generation of miRNA/target prediction algorithms.
Tập 14 Số 7 - Trang 1297-1317 - 2008
The requirement for eukaryotic initiation factor 4A (eIF4A) in translation is in direct proportion to the degree of mRNA 5′ secondary structure
Tập 7 Số 3 - Trang 382-394 - 2001
Translational activation of uncapped mRNAs by the central part of human eIF4G is 5′ end-dependent
Tập 4 Số 7 - Trang 828-836 - 1998
Adenosine 5′-O-(3-thio)triphosphate (ATPγS) is a substrate for the nucleotide hydrolysis and RNA unwinding activities of eukaryotic translation initiation factor eIF4A Whereas ATPγS is often considered a nonhydrolyzable substrate for ATPases, we present evidence that ATPγS is a good substrate for the RNA-stimulated nucleotide hydrolysis and RNA unwinding activities of eIF4A. In the presence of saturating single-stranded poly(U) RNA, eIF4A hydrolyzes ATPγS•Mg and ATP•Mg with similar steady-state parameters (K M NTP•Mg = 66 and 58 μM and k cat = 1.0 and 0.97 min−1 , respectively). ATPγS•Mg also supports catalysis of RNA unwinding within 10-fold of the rate supported by ATP•Mg. The identical steady-state rate parameters, in comparison with the expected difference in the intrinsic rate of hydrolysis for ATP and ATPγS, suggest a nonchemical rate-limiting step for nucleotide hydrolysis. These results raise caution concerning the assumption that ATPγS is a nonhydrolyzable ATP analog and underscore the utility of thio-substituted NTPs as mechanistic probes.
Tập 9 Số 10 - Trang 1180-1187 - 2003
Lentivirus-delivered stable gene silencing by RNAi in primary cells Genome-wide genetic approaches have proven useful for examining pathways of biological significance in model organisms such as Saccharomyces cerevisiae, Drosophila melanogastor, and Caenorhabditis elegans, but similar techniques have proven difficult to apply to mammalian systems. Although manipulation of the murine genome has led to identification of genes and their function, this approach is laborious, expensive, and often leads to lethal phenotypes. RNA interference (RNAi) is an evolutionarily conserved process of gene silencing that has become a powerful tool for investigating gene function by reverse genetics. Here we describe the delivery of cassettes expressing hairpin RNA targeting green fluorescent protein (GFP) using Moloney leukemia virus-based and lentivirus-based retroviral vectors. Both transformed cell lines and primary dendritic cells, normally refractory to transfection-based gene transfer, demonstrated stable silencing of targeted genes, including the tumor suppressor gene TP53 in normal human fibroblasts. This report demonstrates that both Moloney leukemia virus and lentivirus vector-mediated expression of RNAi can achieve effective, stable gene silencing in diverse biological systems and will assist in elucidating gene functions in numerous cell types including primary cells.
Tập 9 Số 4 - Trang 493-501 - 2003
Structure of the RNA inside the vesicular stomatitis virus nucleocapsid
Tập 6 Số 2 - Trang 270-281 - 2000