Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

3' end processing of a long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA.

ABSTRACT: MALAT1 is a long noncoding RNA known to be misregulated in many human cancers. We have identified a highly conserved small RNA of 61 nucleotides originating from the MALAT1 locus that is broadly expressed in human tissues. Although the long MALAT1 transcript localizes to nuclear speckles, the small RNA is found exclusively in the cytoplasm. RNase P cleaves the nascent MALAT1 transcript downstream of a genomically encoded poly(A)-rich tract to simultaneously generate the 3' end of the mature MALAT1 transcript and the 5' end of the small RNA. Enzymes involved in tRNA biogenesis then further process the small RNA, consistent with its adoption of a tRNA-like structure. Our findings reveal a 3' end processing mechanism by which a single gene locus can yield both a stable nuclear-retained noncoding RNA with a short poly(A) tail-like moiety and a small tRNA-like cytoplasmic RNA.

SUBMITTER: Wilusz JE

PROVIDER: S-EPMC2722846 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

3' end processing of a long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA.

Wilusz Jeremy E JE Freier Susan M SM Spector David L DL

Cell 20081101 5

MALAT1 is a long noncoding RNA known to be misregulated in many human cancers. We have identified a highly conserved small RNA of 61 nucleotides originating from the MALAT1 locus that is broadly expressed in human tissues. Although the long MALAT1 transcript localizes to nuclear speckles, the small RNA is found exclusively in the cytoplasm. RNase P cleaves the nascent MALAT1 transcript downstream of a genomically encoded poly(A)-rich tract to simultaneously generate the 3' end of the mature MALA ...[more]

PMID: 19041754

Similar Datasets

Alternative 3'-end processing of long noncoding RNA initiates construction of nuclear paraspeckles.

Project description:Paraspeckles are unique subnuclear structures built around a specific long noncoding RNA, NEAT1, which is comprised of two isoforms produced by alternative 3'-end processing (NEAT1_1 and NEAT1_2). To address the precise molecular processes that lead to paraspeckle formation, we identified 35 paraspeckle proteins (PSPs), mainly by colocalization screening with a fluorescent protein-tagged full-length cDNA library. Most of the newly identified PSPs possessed various putative RNA-binding domains. Subsequent RNAi analyses identified seven essential PSPs for paraspeckle formation. One of the essential PSPs, HNRNPK, appeared to affect the production of the essential NEAT1_2 isoform by negatively regulating the 3'-end polyadenylation of the NEAT1_1 isoform. An in vitro 3'-end processing assay revealed that HNRNPK arrested binding of the CPSF6-NUDT21 (CFIm) complex in the vicinity of the alternative polyadenylation site of NEAT1_1. In vitro binding assays showed that HNRNPK competed with CPSF6 for binding to NUDT21, which was the underlying mechanism to arrest CFIm binding by HNRNPK. This HNRNPK function led to the preferential accumulation of NEAT1_2 and initiated paraspeckle construction with multiple PSPs.

| S-EPMC3474925 | biostudies-literature

ARS2 Regulates Nuclear Paraspeckle Formation through 3'-End Processing and Stability of NEAT1 Long Noncoding RNA.

Project description:Nuclear paraspeckle assembly transcript 1 (NEAT1) is a long noncoding RNA that functions as an essential framework of subnuclear paraspeckle bodies. Of the two isoforms (NEAT1_1 and NEAT1_2) produced by alternative 3'-end RNA processing, the longer isoform, NEAT1_2, plays a crucial role in paraspeckle formation. Here, we demonstrate that the 3'-end processing and stability of NEAT1 RNAs are regulated by arsenic resistance protein 2 (ARS2), a factor interacting with the cap-binding complex (CBC) that binds to the m7G cap structure of RNA polymerase II transcripts. The knockdown of ARS2 inhibited the association between NEAT1 and mammalian cleavage factor I (CFIm), which produces the shorter isoform, NEAT1_1. Furthermore, the knockdown of ARS2 led to the preferential stabilization of NEAT1_2. As a result, NEAT1_2 RNA levels were markedly elevated in ARS2 knockdown cells, leading to an increase in the number of paraspeckles. These results reveal a suppressive role for ARS2 in NEAT1_2 expression and the subsequent formation of paraspeckles.

| S-EPMC6996275 | biostudies-literature

Long noncoding RNA repertoire and targeting by nuclear exosome, cytoplasmic exonuclease, and RNAi in fission yeast.

Project description:Long noncoding RNAs (lncRNAs), which are longer than 200 nucleotides but often unstable, contribute a substantial and diverse portion to pervasive noncoding transcriptomes. Most lncRNAs are poorly annotated and understood, although several play important roles in gene regulation and diseases. Here we systematically uncover and analyze lncRNAs in Schizosaccharomyces pombe. Based on RNA-seq data from twelve RNA-processing mutants and nine physiological conditions, we identify 5775 novel lncRNAs, nearly 4× the previously annotated lncRNAs. The expression of most lncRNAs becomes strongly induced under the genetic and physiological perturbations, most notably during late meiosis. Most lncRNAs are cryptic and suppressed by three RNA-processing pathways: the nuclear exosome, cytoplasmic exonuclease, and RNAi. Double-mutant analyses reveal substantial coordination and redundancy among these pathways. We classify lncRNAs by their dominant pathway into cryptic unstable transcripts (CUTs), Xrn1-sensitive unstable transcripts (XUTs), and Dicer-sensitive unstable transcripts (DUTs). XUTs and DUTs are enriched for antisense lncRNAs, while CUTs are often bidirectional and actively translated. The cytoplasmic exonuclease, along with RNAi, dampens the expression of thousands of lncRNAs and mRNAs that become induced during meiosis. Antisense lncRNA expression mostly negatively correlates with sense mRNA expression in the physiological, but not the genetic conditions. Intergenic and bidirectional lncRNAs emerge from nucleosome-depleted regions, upstream of positioned nucleosomes. Our results highlight both similarities and differences to lncRNA regulation in budding yeast. This broad survey of the lncRNA repertoire and characteristics in S. pombe, and the interwoven regulatory pathways that target lncRNAs, provides a rich framework for their further functional analyses.

| S-EPMC6097657 | biostudies-literature

Genome-wide screen uncovers novel pathways for tRNA processing and nuclear-cytoplasmic dynamics.

Project description:Transfer ribonucleic acids (tRNAs) are essential for protein synthesis. However, key gene products involved in tRNA biogenesis and subcellular movement remain to be discovered. We conducted the first comprehensive unbiased analysis of the role of nearly an entire proteome in tRNA biology and describe 162 novel and 12 previously known Saccharomyces cerevisiae gene products that function in tRNA processing, turnover, and subcellular movement. tRNA nuclear export is of particular interest because it is essential, but the known tRNA exporters (Los1 [exportin-t] and Msn5 [exportin-5]) are unessential. We report that mutations of CRM1 (Exportin-1), MEX67/MTR2 (TAP/p15), and five nucleoporins cause accumulation of unspliced tRNA, a hallmark of defective tRNA nuclear export. CRM1 mutation genetically interacts with los1Δ and causes altered tRNA nuclear-cytoplasmic distribution. The data implicate roles for the protein and mRNA nuclear export machineries in tRNA nuclear export. Mutations of genes encoding actin cytoskeleton components and mitochondrial outer membrane proteins also cause accumulation of unspliced tRNA, likely due to defective splicing on mitochondria. Additional gene products, such as chromatin modification enzymes, have unanticipated effects on pre-tRNA end processing. Thus, this genome-wide screen uncovered putative novel pathways for tRNA nuclear export and extensive links between tRNA biology and other aspects of cell physiology.

| S-EPMC4699390 | biostudies-literature

The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation.

Project description:Alternative splicing (AS) of pre-mRNA is utilized by higher eukaryotes to achieve increased transcriptome and proteomic complexity. The serine/arginine (SR) splicing factors regulate tissue- or cell-type-specific AS in a concentration- and phosphorylation-dependent manner. However, the mechanisms that modulate the cellular levels of active SR proteins remain to be elucidated. In the present study, we provide evidence for a role for the long nuclear-retained regulatory RNA (nrRNA), MALAT1 in AS regulation. MALAT1 interacts with SR proteins and influences the distribution of these and other splicing factors in nuclear speckle domains. Depletion of MALAT1 or overexpression of an SR protein changes the AS of a similar set of endogenous pre-mRNAs. Furthermore, MALAT1 regulates cellular levels of phosphorylated forms of SR proteins. Taken together, our results suggest that MALAT1 regulates AS by modulating the levels of active SR proteins. Our results further highlight the role for an nrRNA in the regulation of gene expression.

| S-EPMC4158944 | biostudies-literature

Stem-loop RNA labeling can affect nuclear and cytoplasmic mRNA processing.

Project description:The binding of sequence-specific RNA-interacting proteins, such as the bacteriophage MS2 or PP7 coat proteins, to their corresponding target sequences has been extremely useful and widely used to visualize single mRNAs in vivo. However, introduction of MS2 stem-loops into yeast mRNAs has recently been shown to lead to the accumulation of RNA fragments, suggesting that the loops impair mRNA decay. This result was questioned, because fragment occurrence was mainly assessed using ensemble methods, and their cellular localization and its implications had not been addressed on a single transcript level. Here, we demonstrate that the introduction of either MS2 stem-loops (MS2SL) or PP7 stem-loops (PP7SL) can affect the processing and subcellular localization of mRNA. We use single-molecule fluorescence in situ hybridization (smFISH) to determine the localization of three independent mRNAs tagged with the stem-loop labeling systems in glucose-rich and glucose starvation conditions. Transcripts containing MS2SL or PP7SL display aberrant localization in both the nucleus and the cytoplasm. These defects are most prominent in glucose starvation conditions, with nuclear mRNA processing being altered and stem-loop fragments abnormally enriching in processing bodies (PBs). The mislocalization of SL-containing RNAs is independent of the presence of the MS2 or PP7 coat protein (MCP or PCP).

| S-EPMC5238788 | biostudies-literature

A long nuclear-retained non-coding RNA regulates synaptogenesis by modulating gene expression.

Project description:A growing number of long nuclear-retained non-coding RNAs (ncRNAs) have recently been described. However, few functions have been elucidated for these ncRNAs. Here, we have characterized the function of one such ncRNA, identified as metastasis-associated lung adenocarcinoma transcript 1 (Malat1). Malat1 RNA is expressed in numerous tissues and is highly abundant in neurons. It is enriched in nuclear speckles only when RNA polymerase II-dependent transcription is active. Knock-down studies revealed that Malat1 modulates the recruitment of SR family pre-mRNA-splicing factors to the transcription site of a transgene array. DNA microarray analysis in Malat1-depleted neuroblastoma cells indicates that Malat1 controls the expression of genes involved not only in nuclear processes, but also in synapse function. In cultured hippocampal neurons, knock-down of Malat1 decreases synaptic density, whereas its over-expression results in a cell-autonomous increase in synaptic density. Our results suggest that Malat1 regulates synapse formation by modulating the expression of genes involved in synapse formation and/or maintenance.

| S-EPMC2944070 | biostudies-literature

Assessment Of Long Noncoding RNA CCAT1 In Colorectal Cancer Patients

Project description:1. Evaluate the diagnostic value of long noncoding RNA (CCAT1) expression by RT-PCR in peripheral blood in colorectal cancer patients versus normal healthy control personal. 2. Evaluate the clinical utility of detecting long noncoding RNA (CCAT1) expression in diagnosis of colorectal cancer patients & its relation to tumor staging. 3. Evaluate the clinical utility of detecting long noncoding RNA (CCAT1) expression in precancerous colorectal diseases. 4. Compare long noncoding RNA (CCAT1) expression with traditional marker; carcinoembryonic antigen (CEA) and Carbohydrate antigen 19-9 (CA19-9) in diagnosis of colorectal cancer.

| 2330122 | ecrin-mdr-crc

Long noncoding RNAs: Re-writing dogmas of RNA processing and stability.

Project description:Most of the human genome is transcribed, yielding a complex network of transcripts that includes tens of thousands of long noncoding RNAs. Many of these transcripts have a 5' cap and a poly(A) tail, yet some of the most abundant long noncoding RNAs are processed in unexpected ways and lack these canonical structures. Here, I highlight the mechanisms by which several of these well-characterized noncoding RNAs are generated, stabilized, and function. The MALAT1 and MEN ? (NEAT1_2) long noncoding RNAs each accumulate to high levels in the nucleus, where they play critical roles in cancer progression and the formation of nuclear paraspeckles, respectively. Nevertheless, MALAT1 and MEN ? are not polyadenylated as the tRNA biogenesis machinery generates their mature 3' ends. In place of a poly(A) tail, these transcripts are stabilized by highly conserved triple helical structures. Sno-lncRNAs likewise lack poly(A) tails and instead have snoRNA structures at their 5' and 3' ends. Recent work has additionally identified a number of abundant circular RNAs generated by the pre-mRNA splicing machinery that are resistant to degradation by exonucleases. As these various transcripts use non-canonical strategies to ensure their stability, it is becoming increasingly clear that long noncoding RNAs may often be regulated by unique post-transcriptional control mechanisms. This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy1, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa.

| S-EPMC4676738 | biostudies-literature

An RNA-protein complex links enhanced nuclear 3' processing with cytoplasmic mRNA stabilization.

Project description:Post-transcriptional controls are critical to gene regulation. These controls are frequently based on sequence-specific binding of trans-acting proteins to cis-acting motifs on target RNAs. Prior studies have revealed that the KH-domain protein, ?CP, binds to a 3' UTR C-rich motif of h?-globin mRNA and contributes to its cytoplasmic stability. Here, we report that this 3' UTR ?CP complex regulates the production of mature ?-globin mRNA by enhancing 3' processing of the h?-globin transcript. We go on to demonstrate that this nuclear activity reflects enhancement of both the cleavage and the polyadenylation reactions and that ?CP interacts in vivo with core components of the 3' processing complex. Consistent with its nuclear processing activity, our studies reveal that ?CP assembles co-transcriptionally at the h?-globin chromatin locus and that this loading is selectively enriched at the 3' terminus of the gene. The demonstrated linkage of nuclear processing with cytoplasmic stabilization via a common RNA-protein complex establishes a basis for integration of sequential controls critical to robust and sustained expression of a target mRNA.

| S-EPMC3155305 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data