RNA processing genes characterize RNA splicing and further stratify colorectal cancer

Several biologically important examples of posttranscriptionally regulated genes have recently been described (T. Gerster, D. Picard, and W. Schaffner, Cell 45:45-52, 1986; R. Reeves, T.S. Elton, M.S. Nissen, D. Lehn, and K.R. Johnson, Proc. Natl. Acad. Sci. USA 84:6531-6535, 1987; H.A. Young, L. Varesio, and P. Hwu, Mol. Cell. Biol. 6:2253-2256, 1986). Little is known, however, regarding sequences that mediate posttranscriptional RNA stability. Characterization in our laboratory of a mutant murine B lymphoma, M12.C3, revealed a posttranscriptional defect affecting the synthesis of a major histocompatibility complex class II gene (A beta d) whose product normally controls both the specificity and magnitude of the immune response. Molecular studies revealed that the mutation responsible for diminished A beta d gene expression was an intronic deletion of 10 base pairs (bp) located 99 bp 5' of the third exon. This deletion lies in a region not known to be critical for accurate and efficient splicing. Furthermore, sequence analysis of amplified A beta-specific cDNA demonstrated that the small number of A beta d transcripts produced in the mutant cells was correctly spliced. It appears that the mechanism by which this intronic 10-bp deletion acts to decrease RNA stability is unlikely to be at the level of RNA splicing.

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Rearrangements of intranuclear structures involved in RNA processing in response to adenovirus infection

Journal of Cell Science ◽

10.1242/jcs.107.6.1457 ◽

1994 ◽

Vol 107 (6) ◽

pp. 1457-1468 ◽

Cited By ~ 2

Author(s):

F. Puvion-Dutilleul ◽

J.P. Bachellerie ◽

N. Visa ◽

E. Puvion

Keyword(s):

Rna Processing ◽

Rna Splicing ◽

Specific Binding ◽

Viral Rna ◽

Nuclear Transformation ◽

Adenovirus Infection ◽

Storage Site ◽

Single Stranded Dna ◽

Viral Genomes ◽

Interchromatin Granules

We have studied in HeLa cells at the electron microscope level the response to adenovirus infection of the RNA processing machinery. Components of the spliceosomes were localized by in situ hybridization with biotinylated U1 and U2 DNA probes and by immunolabeling with Y12 anti-Sm monoclonal antibody, whereas poly(A)+ RNAs were localized by specific binding of biotinylated poly(dT) probe. At early stages of nuclear transformation, the distribution of small nuclear RNPs was similar to that previously described in non-infected nuclei (Visa, N., Puvion-Dutilleul, F., Bachellerie, J.P. and Puvion, E., Eur. J. Cell Biol. 60, 308–321, 1993; Visa, N., Puvion-Dutilleul, F., Harper, F., Bachellerie, J. P. and Puvion, E., Exp. Cell Res. 208, 19–34, 1993). As the infection progresses, the large virus-induced inclusion body consists of a central storage site of functionally inactive viral genomes surrounded by a peripheral shell formed by clusters of interchromatin granules, compact rings and a fibrillogranular network in which are embedded the viral single-stranded DNA accumulation sites. Spliceosome components and poly(A)+ RNAs were then exclusively detected over the clusters of interchromatin granules and the fibrillogranular network whereas the viral single-stranded DNA accumulation sites and compact rings remained unlabeled, thus appearing to not be directly involved in splicing. Our data, therefore, suggest that the fibrillogranular network, in addition to being the site of viral transcription, is also a major site of viral RNA splicing. Like the clusters of interchromatin granules, which had been already involved in spliceosome assembly, they could also have a role in the sorting of viral spliced polyadenylated mRNAs before export to the cytoplasm. The compact rings, which contain non-polyadenylated viral RNA, might accumulate the non-used portions of the viral transcripts resulting from differential poly(A)+ site selection.

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The Regulatory Role of Both MBNL1 and MBNL1-AS1 in Several Common Cancers

Current Pharmaceutical Design ◽

10.2174/1381612827666210830110732 ◽

2021 ◽

Vol 27 ◽

Author(s):

Qi Zhang ◽

Yinxin Wu ◽

Jinlan Chen ◽

Yuxuan Cai ◽

Bei Wang ◽

...

Keyword(s):

Breast Cancer ◽

Colorectal Cancer ◽

Gastric Cancer ◽

Lung Cancer ◽

Overall Survival ◽

Survival Rate ◽

Rna Splicing ◽

Metabolic Regulation ◽

Overall Survival Rate

Background: MBNL1, a protein encoded by q25 gene on chromosome 3, belongs to the tissue-specific RNA metabolic regulation family, which controls RNA splicing.[1]MBNL1 formed in the process of development drive large transcriptomic changes in cell differentiation,[2] it serves as a kind of tumor differentiation inhibitory factor.MBNL1 has a close relationship with cancer, comprehensive analysis, [3]found that breast cancer, leukemia, stomach cancer, esophageal adenocarcinoma, glial cell carcinoma and another common tumor in the cut, and cut in Huntington's disease. But MBNL1 plays a promoting role in cervical cancer, is contradictory in colorectal cancer, It promotes colorectal cancer cell proliferation, On the other hand, it inhibits its metastasis, so it is an important physiological marker in many cancers. When we integrated the role of MBNL1 protein in various tumors, we found that its antisense RNA, MBNL1-AS1, had a good inhibitory effect in several colorectal cancer, non-small cell lung cancer, and gastric cancer. Objective: To elucidate the expression of MBNL1 and MBNL1-AS1 in various tumors, and to search for their physiological markers. Methods: It was searched by the PUMUB system and summarized its expression in various cancers. Results: MBNL1 was down-regulated, leukemia, breast cancer, glioblastoma, gastric cancer, overall survival rate, recurrence, metastasis increased. While the metastasis of colon cancer decreased, proliferation was promoted, and the effect of both was promoted for cervical cancer.MBNL1-AS1 was down-regulated, and the overall survival rate, recurrence, and metastasis of lung cancer, colorectal cancer, and bladder cancer increased. Conclusion: MBNL1 may be an important regulator of cancer, and MBNL1-AS1 is a better tumor suppressor.

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Aberrant RNA splicing in thehMSH2 gene: Molecular identification of three aberrant RNA in Scottish patients with colorectal cancer in the West of Scotland

American Journal of Medical Genetics ◽

10.1002/1096-8628(20001106)95:1<49::aid-ajmg10>3.0.co;2-p ◽

2000 ◽

Vol 95 (1) ◽

pp. 49-52 ◽

Cited By ~ 3

Author(s):

Abdoreza Davoodi-Semiromi ◽

George W. Lanyon ◽

Rosemary Davidson ◽

Michael J. Connor

Keyword(s):

Colorectal Cancer ◽

Molecular Identification ◽

Rna Splicing ◽

The West ◽

Aberrant Rna

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RNA processing genes characterize RNA splicing and further stratify lower-grade glioma

JCI Insight ◽

10.1172/jci.insight.130591 ◽

2019 ◽

Cited By ~ 3

Author(s):

Rui-Chao Chai ◽

Yi-Ming Li ◽

Ke-Nan Zhang ◽

Yu-Zhou Chang ◽

Yu-Qing Liu ◽

...

Keyword(s):

Rna Processing ◽

Rna Splicing ◽

Lower Grade ◽

Lower Grade Glioma

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Mitotic noncoding RNA processing promotes kinetochore and spindle assembly in Xenopus

The Journal of Cell Biology ◽

10.1083/jcb.201604029 ◽

2016 ◽

Vol 214 (2) ◽

pp. 133-141 ◽

Cited By ~ 40

Author(s):

Andrew W. Grenfell ◽

Rebecca Heald ◽

Magdalena Strzelecka

Keyword(s):

Rna Processing ◽

Rna Splicing ◽

Transcription Initiation ◽

Noncoding Rna ◽

Spindle Assembly ◽

Aurora B ◽

Mitotic Chromosomes ◽

Mitotic Kinase ◽

Egg Extracts ◽

Xenopus Egg Extracts

Transcription at the centromere of chromosomes plays an important role in kinetochore assembly in many eukaryotes, and noncoding RNAs contribute to activation of the mitotic kinase Aurora B. However, little is known about how mitotic RNA processing contributes to spindle assembly. We found that inhibition of transcription initiation or RNA splicing, but not translation, leads to spindle defects in Xenopus egg extracts. Spliceosome inhibition resulted in the accumulation of high molecular weight centromeric transcripts, concomitant with decreased recruitment of the centromere and kinetochore proteins CENP-A, CENP-C, and NDC80 to mitotic chromosomes. In addition, blocking transcript synthesis or processing during mitosis caused accumulation of MCAK, a microtubule depolymerase, on the spindle, indicating misregulation of Aurora B. These findings suggest that co-transcriptional recruitment of the RNA processing machinery to nascent mitotic transcripts is an important step in kinetochore and spindle assembly and challenge the idea that RNA processing is globally repressed during mitosis.

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Viral-mediated ubiquitination impacts interactions of host proteins with viral RNA and promotes viral RNA processing

10.1101/2020.06.05.136671 ◽

2020 ◽

Author(s):

Christin Herrmann ◽

Joseph M. Dybas ◽

Jennifer C. Liddle ◽

Alexander M Price ◽

Katharina E. Hayer ◽

...

Keyword(s):

Rna Processing ◽

Rna Splicing ◽

Rna Binding ◽

Rna Binding Proteins ◽

Virus Production ◽

Viral Rna ◽

Cellular Processes ◽

Early Proteins ◽

Ubiquitin Ligase Complex ◽

Hnrnp C

ABSTRACTViruses promote infection by hijacking host ubiquitin machinery to counteract or redirect cellular processes. Adenovirus encodes two early proteins, E1B55K and E4orf6, that together co-opt a cellular ubiquitin ligase complex to overcome host defenses and promote virus production. Adenovirus mutants lacking E1B55K or E4orf6 display defects in viral RNA processing and protein production, but previously identified substrates of the redirected ligase do not explain these phenotypes. Here we used a quantitative proteomics approach to identify substrates of E1B55K/E4orf6-mediated ubiquitination that facilitate RNA processing. While all currently known cellular substrates of E1B55K/E4orf6 are degraded by the proteasome, we uncovered RNA-binding proteins (RBPs) as high-confidence substrates which are not decreased in overall abundance. We focused on two RBPs, RALY and hnRNP-C, which we confirm are ubiquitinated without degradation. Knockdown of RALY and hnRNP-C increased levels of viral RNA splicing, protein abundance, and progeny production during infection with E1B55K-deleted virus. Furthermore, infection with virus deleted for E1B55K resulted in increased interaction of hnRNP-C with viral RNA, and attenuation of viral RNA processing. These data suggest viral-mediated ubiquitination of RALY and hnRNP-C relieves a restriction on viral RNA processing, revealing an unexpected role for non-degradative ubiquitination in manipulation of cellular processes during virus infection.

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Ribosomal Protein Rpl22 Regulates Development and Transformation Via Altering RNA Processing

Blood ◽

10.1182/blood.v128.22.3878.3878 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3878-3878 ◽

Cited By ~ 1

Author(s):

Minshi Wang ◽

Zheng Ser ◽

Shuyun Rao ◽

Shawn Fahl ◽

Yong Zhang ◽

...

Keyword(s):

Alternative Splicing ◽

Rna Processing ◽

Rna Splicing ◽

Ribosome Biogenesis ◽

Conflicts Of Interest ◽

Lymphoblastic Leukemia ◽

Read Depth ◽

Mrna Splicing ◽

Transformation Potential ◽

Morpholino Oligonucleotides

Abstract Although it has long been reported that mutations in ribosome proteins (RP) are associated with increased cancer risk in humans, the molecular basis why which RP mutations do so remains unclear. Nevertheless, the prevailing view is that RP mutations, such as Rps19, are thought to alter transformation potential through general impairment of ribosome biogenesis or function. Importantly, recent observations are beginning to challenge this notion as too simplistic. We have determined that the RP, Rpl22, is not essential for ribosome biogenesis or global protein synthesis; however, its inactivation impairs the development of normal T lymphocytes and increases their transformation potential. Indeed, RPL22 is inactivated in human T acute lymphoblastic leukemia (T-ALL) and this is associated with reduced survival. Moreover, Rpl22-deficiency accelerates development of leukemia in a myristylated Akt2 transgenic (MyrAkt2 Tg) mouse model of T-ALL. To gain insight into how Rpl22 inactivation facilitates development of leukemia, we are performing unbiased transcriptomic and proteomic analysis on Rpl22+/+ and Rpl22-/- thymic lymphomas arising in the MyrAkt2 Tg model, and in an Rpl22-/- lymphoma reconstituted with Rpl22. Interestingly, relatively few changes in mRNA transcript read depth were observed; however, substantial differences in the proteome were observed. Pathway analysis revealed that the loss of Rpl22 altered the expression of proteins regulating RNA-processing, in particular RNA-splicing. Interestingly, interrogation of the transrciptome data for alternative splicing revealed that alterations in exon usage. The ability of Rpl22 to influence splicing appears to be conserved across species as alternative splicing was also observed in zebrafish embryos in which Rpl22 was knocked down using morpholino oligonucleotides. Consequently, we hypothesize that Rpl22 regulates biological events through its ability of binding to RNA targets, and controlling the expression of their protein products at least in part through altering mRNA splicing. How Rpl22 changes mRNA splicing pattern is currently under investigation. Disclosures No relevant conflicts of interest to declare.

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