Abstract:
:RBM10 is an RNA binding protein and alternative splicing regulator frequently mutated in lung adenocarcinomas. Recent results indicate that RBM10 inhibits proliferation of lung cancer cells by promoting skipping of exon 9 of the gene NUMB, a frequent alternative splicing change in lung cancer generating a negative regulator of Notch signaling. Complementing these observations, we show that knock down of RBM10 in human cancer cells enhances growth of mouse tumor xenografts, confirming that RBM10 acts as a tumor suppressor, while knock down of an oncogenic mutant version of RBM10 reduces xenograft tumor growth. A RBM10 mutation found in lung cancer cells, V354E, disrupts RBM10-mediated regulation of NUMB alternative splicing, inducing the cell proliferation-promoting isoform. We now show that 2 natural RBM10 isoforms that differ by the presence or absence of V354 in the second RNA Recognition Motif (RRM2), display similar regulatory effects on NUMB alternative splicing, suggesting that V354E actively disrupts RBM10 activity. Structural modeling localizes V354 in the outside surface of one α-helix opposite to the RNA binding surface of RBM10, and we show that the mutation does not compromise binding of the RRM2 domain to NUMB RNA regulatory sequences. We further show that other RBM10 mutations found in lung adenocarcinomas also compromise regulation of NUMB exon 9. Collectively, our previous and current results reveal that RBM10 is a tumor suppressor that represses Notch signaling and cell proliferation through the regulation of NUMB alternative splicing.
journal_name
RNA Bioljournal_title
RNA biologyauthors
Hernández J,Bechara E,Schlesinger D,Delgado J,Serrano L,Valcárcel Jdoi
10.1080/15476286.2016.1144004subject
Has Abstractpub_date
2016-01-01 00:00:00pages
466-72issue
4eissn
1547-6286issn
1555-8584journal_volume
13pub_type
杂志文章相关文献
RNA Biology文献大全abstract::At low temperatures the Escherichia coli rpoS mRNA, encoding the stationary phase sigma factor RpoS, forms an intramolecular secondary structure (iss) that impedes translation initiation. Under these conditions the small RNA DsrA, which is stabilzed by Hfq, forms a duplex with rpoS mRNA sequences opposite of the ribos...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.27100
更新日期:2013-12-01 00:00:00
abstract::Eukaryotic gene expression must be coordinated for the proper functioning of biological processes. This coordination can be achieved both at the transcriptional and post-transcriptional levels. In both cases, regulatory sequences placed at either promoter regions or on UTRs function as markers recognized by regulators...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.7116
更新日期:2008-10-01 00:00:00
abstract::In plants, Potato spindle tuber viroid (PSTVd) replication triggers post-transcriptional gene silencing (PTGS) and RNA-directed DNA methylation (RdDM) of homologous RNA and DNA sequences, respectively. PTGS predominantly occurs in the cytoplasm, but nuclear PTGS has been also reported. In this study, we investigated w...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2015.1017216
更新日期:2015-01-01 00:00:00
abstract::The Hedgehog (HH) signaling pathway has important roles in tumorigenesis and in embryonal patterning. The Glioma-associated oncogene 1 (GLI1) is a key molecule in HH signaling, acting as a transcriptional effector and, moreover, is considered to be a potential therapeutic target for several types of cancer. To extend ...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.23343
更新日期:2013-02-01 00:00:00
abstract::Nonsense-mediated decay (NMD) is a RNA surveillance pathway that degrades subsets of normal and aberrant mRNAs. Mutations that perturb NMD cause neurological disorders in humans, suggesting that NMD has roles in the brain. Recently, it was shown that NMD is repressed during neural development to allow for the stabiliz...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.9.1.18010
更新日期:2012-01-01 00:00:00
abstract::With a minimal (250-400 nt), non-protein-coding, circular RNA genome, viroids rely on sequence/structural motifs for replication and colonization of their host plants. These motifs are embedded in a compact secondary structure whose elucidation is crucial to understand how they function. Viroid RNA structure has been ...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2016.1223005
更新日期:2017-08-03 00:00:00
abstract::MicroRNAs (miRNAs) are a class of naturally occurring, small, non-coding RNAs that control gene expression during development,normal cell function and disease. Although there is emerging evidence that some miRNAs can function as oncogenes or tumor suppressors, there is limited understanding of the role of miRNAs in ca...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.6.5.10079
更新日期:2009-11-01 00:00:00
abstract::Earlier we have demonstrated the presence of internal ribosome entry site (IRES) within tumor suppressor p53 mRNA. Here we have mapped the putative secondary structure of p53- IRES RNA using information from chemical probing and nuclease mapping experiments. Additionally, the secondary structure of the IRES element of...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.8.1.14260
更新日期:2011-01-01 00:00:00
abstract::Post-transcriptional control of gene expression is mediated via RNA-binding proteins (RBPs) that interact with mRNAs in a combinatorial fashion. While recent global RNA interactome capture experiments expanded the repertoire of cellular RBPs quiet dramatically, little is known about the assembly of RBPs on particular ...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2019.1662268
更新日期:2020-01-01 00:00:00
abstract::YchF is one of two universally conserved GTPases with unknown cellular function. As a first step toward elucidating YchF's cellular role, we performed a detailed biochemical characterization of the protein from Escherichia coli. Our data from fluorescence titrations not only confirmed the surprising finding that YchFE...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.22131
更新日期:2012-10-01 00:00:00
abstract::Studies on the regulation of gene expression in eukaryotes in the past 20 years have consistently revealed increasing levels of complexity. Thirty years ago it seemed that we had understood the basic principles of gene regulation in eukaryotes. It was thought that regulation of transcription was the first and most imp...
journal_title:RNA biology
pub_type:
doi:10.4161/rna.28037
更新日期:2014-01-01 00:00:00
abstract::MicroRNAs are essential for spermatogenesis. However, the stage-specific requirements for particular miRNAs in the male mammalian germ line remain largely uncharacterized. The miR-34 family is, to date, the only miRNA proven to be necessary for the production of sperm in mammals, though its germline roles are poorly u...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2016.1270002
更新日期:2017-02-01 00:00:00
abstract::In metazoan organisms, alternative splicing is a central mechanism for the regulation of gene expression. However, many questions remain about the underlying molecular mechanisms. Our recent work suggests that U1 snRNP-independent premRNA splicing occurs in humans, which contributes to the regulation of alternative sp...
journal_title:RNA biology
pub_type: 杂志文章,评审
doi:10.4161/rna.6.4.9318
更新日期:2009-09-01 00:00:00
abstract::While disruption of alternative splicing underlies many diseases, modulation of splicing using antisense oligonucleotides (AONs) can have therapeutic implications. The most notable example is Duchenne muscular dystrophy (DMD), where antisense-mediated exon skipping can restore the open reading frame and allow the synt...
journal_title:RNA biology
pub_type: 杂志文章,评审
doi:10.4161/rna.7.4.12264
更新日期:2010-07-01 00:00:00
abstract::RNA-binding proteins (RBPs) are key regulators of posttranscriptional processes such as RNA maturation, localization, turnover and translation. Despite their dysregulation in various diseases including cancer, the landscape of RBP expression in human cancer has not been well elucidated. Here, we built a comprehensive ...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2019.1673657
更新日期:2020-02-01 00:00:00
abstract::Polycystic ovary syndrome (PCOS) causes anovulatory infertility in women of reproductive age, but etiopathogenesis of PCOS remains undetermined. Taurine up-regulated 1 (TUG1), an evolutionarily conserved long non-coding RNA, performs various biological functions; however, the role of TUG1 in PCOS remains unclear. Here...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2020.1783850
更新日期:2020-12-01 00:00:00
abstract::Ribosome biogenesis is an essential process initiated in the nucleolus. In eukaryotes, multiple ribosome biogenesis factors (RBFs) can be found in the nucleolus, the nucleus and in the cytoplasm. They act in processing, folding and modification of the pre-ribosomal (r)RNAs, incorporation of ribosomal proteins (RPs), e...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2016.1154252
更新日期:2016-01-01 00:00:00
abstract::The question of how cysteinyl-tRNA(Cys) is synthesized in organisms that lack a canonical cysteinyl-tRNA synthetase (CysRS) is an important open question in understanding protein synthesis. The prolyl-tRNA synthetase (ProRS) of wide ranging organisms has the ability to mis-activate cysteine without editing. This raise...
journal_title:RNA biology
pub_type: 杂志文章
doi:
更新日期:2004-05-01 00:00:00
abstract::Ribosome biogenesis drives cell growth and proliferation, but mechanisms that modulate this process remain poorly understood. For a long time, small rRNA sequences have been widely treated as non-specific degradation products and neglected as garbage sequences. Recently, we identified a new class of antisense ribosoma...
journal_title:RNA biology
pub_type: 杂志文章,评审
doi:10.1080/15476286.2017.1341034
更新日期:2017-11-02 00:00:00
abstract::Circular RNAs (circRNAs) are closely associated with the development of non-small cell lung cancer (NSCLC); however, it is still unclear whether circular RNA circ-LDLRAD3 participated in the regulation of NSCLC progression. In this study, we found that circ-LDLRAD3 was high-expressed and miR-137 was low-expressed in N...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2020.1789819
更新日期:2020-12-01 00:00:00
abstract::Myocyte enhancer factor 2c (MEF2C) is the MADS-box type transcription factor involved in the differentiation of cardiac and skeletal muscle and synaptic formation. Alternatively spliced transcripts of the MEF2C gene were proven to encode isoforms which exert distinct functions in transcriptional regulation. During the...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2015.1017213
更新日期:2015-01-01 00:00:00
abstract::Oncogenic viruses are associated with approximately 15% of human cancers. In viral infections, microRNAs play an important role in host-pathogen interactions. miR-21 is a highly conserved non-coding RNA that not only regulates the development of oncogenic viral diseases, but also responds to the regulation of intracel...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2021.1880756
更新日期:2021-01-27 00:00:00
abstract::Non-coding RNA (ncRNA) molecules have fundamental roles in cells and many are also stable in body fluids as extracellular RNAs. In this study, we used RNA sequencing (RNA-seq) to investigate the profile of small non-coding RNA (sncRNA) in human serum. We analyzed 10 billion Illumina reads from 477 serum samples, inclu...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2017.1403003
更新日期:2018-02-01 00:00:00
abstract::microRNAs (miRNAs) play significant regulatory roles in gene expression at the post-transcriptional level. This includes modulating processes such as development, immunity, cancer, and host-pathogen interactions. It was recently shown that the phylogenetically deeply conserved miRNA, miR-8, plays a role in maintaining...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.25481
更新日期:2013-08-01 00:00:00
abstract::Seryl-tRNA synthetase (SerRS) catalyzes the ligation of serine to the 3'-end of serine tRNA (tRNA(Ser)), which is typical of the type-2 tRNAs characterized by a long extra arm. The SerRSs are divided into two types, the archaeal/eukaryal and bacterial types. In this study, we solved the crystal structures of the SerRS...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.5.3.6876
更新日期:2008-07-01 00:00:00
abstract::5-fluorouracil (5-FU) was isolated as an inhibitor of thymidylate synthase, which is important for DNA synthesis. The drug was later found to also affect the conserved 3'-5' exoribonuclease EXOSC10/Rrp6, a catalytic subunit of the RNA exosome that degrades and processes protein-coding and non-coding transcripts. Work ...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2019.1581596
更新日期:2019-06-01 00:00:00
abstract::Significant structural and mechanistic similarities between the spliceosomal snRNAs and catalytically critical domains of self-splicing group II introns have led to the hypothesis that the spliceosomes and group II introns may be evolutionarily related. We have previously shown that in vitro-transcribed, protein-free ...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.8.3.15386
更新日期:2011-05-01 00:00:00
abstract::The tight gene expression regulation controls the development and pathogenesis of human malaria parasite Plasmodium falciparum throughout the complex life cycle. Recent studies have revealed the pervasive nascent transcripts in the genome of P. falciparum, suggesting the existence of a hidden transcriptome involved in...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2020.1732032
更新日期:2020-06-01 00:00:00
abstract::Population differences observed for complex traits may be attributed to the combined effect of socioeconomic, environmental, genetic and epigenetic factors. To better understand population differences in complex traits, genome-wide genetic and gene expression differences among ethnic populations have been studied. Her...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.8.4.16029
更新日期:2011-07-01 00:00:00
abstract::Human Enterovirus 71 (EV71) is an emerging pathogen of infectious disease and a serious threat to public health. Currently, there are no antivirals or vaccines to slow down or prevent EV71 infections, thus underscoring the urgency to better understand mechanisms of host-enterovirus interactions. EV71 uses a type I int...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.25107
更新日期:2013-07-01 00:00:00