Cargando…

The Conserved Intronic Cleavage and Polyadenylation Site of CstF-77 Gene Imparts Control of 3′ End Processing Activity through Feedback Autoregulation and by U1 snRNP

The human gene encoding the cleavage/polyadenylation (C/P) factor CstF-77 contains 21 exons. However, intron 3 (In3) accounts for nearly half of the gene region, and contains a C/P site (pA) with medium strength, leading to short mRNA isoforms with no apparent protein products. This intron contains...

Descripción completa

Detalles Bibliográficos
Autores principales: Luo, Wenting, Ji, Zhe, Pan, Zhenhua, You, Bei, Hoque, Mainul, Li, Wencheng, Gunderson, Samuel I., Tian, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708835/
https://www.ncbi.nlm.nih.gov/pubmed/23874216
http://dx.doi.org/10.1371/journal.pgen.1003613
_version_ 1782276669751427072
author Luo, Wenting
Ji, Zhe
Pan, Zhenhua
You, Bei
Hoque, Mainul
Li, Wencheng
Gunderson, Samuel I.
Tian, Bin
author_facet Luo, Wenting
Ji, Zhe
Pan, Zhenhua
You, Bei
Hoque, Mainul
Li, Wencheng
Gunderson, Samuel I.
Tian, Bin
author_sort Luo, Wenting
collection PubMed
description The human gene encoding the cleavage/polyadenylation (C/P) factor CstF-77 contains 21 exons. However, intron 3 (In3) accounts for nearly half of the gene region, and contains a C/P site (pA) with medium strength, leading to short mRNA isoforms with no apparent protein products. This intron contains a weak 5′ splice site (5′SS), opposite to the general trend for large introns in the human genome. Importantly, the intron size and strengths of 5′SS and pA are all highly conserved across vertebrates, and perturbation of these parameters drastically alters intronic C/P. We found that the usage of In3 pA is responsive to the expression level of CstF-77 as well as several other C/P factors, indicating it attenuates the expression of CstF-77 via a negative feedback mechanism. Significantly, intronic C/P of CstF-77 pre-mRNA correlates with global 3′UTR length across cells and tissues. In addition, inhibition of U1 snRNP also leads to regulation of the usage of In3 pA, suggesting that the C/P activity in the cell can be cross-regulated by splicing, leading to coordination between these two processes. Importantly, perturbation of CstF-77 expression leads to widespread alternative cleavage and polyadenylation (APA) and disturbance of cell proliferation and differentiation. Thus, the conserved intronic pA of the CstF-77 gene may function as a sensor for cellular C/P and splicing activities, controlling the homeostasis of CstF-77 and C/P activity and impacting cell proliferation and differentiation.
format Online
Article
Text
id pubmed-3708835
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-37088352013-07-19 The Conserved Intronic Cleavage and Polyadenylation Site of CstF-77 Gene Imparts Control of 3′ End Processing Activity through Feedback Autoregulation and by U1 snRNP Luo, Wenting Ji, Zhe Pan, Zhenhua You, Bei Hoque, Mainul Li, Wencheng Gunderson, Samuel I. Tian, Bin PLoS Genet Research Article The human gene encoding the cleavage/polyadenylation (C/P) factor CstF-77 contains 21 exons. However, intron 3 (In3) accounts for nearly half of the gene region, and contains a C/P site (pA) with medium strength, leading to short mRNA isoforms with no apparent protein products. This intron contains a weak 5′ splice site (5′SS), opposite to the general trend for large introns in the human genome. Importantly, the intron size and strengths of 5′SS and pA are all highly conserved across vertebrates, and perturbation of these parameters drastically alters intronic C/P. We found that the usage of In3 pA is responsive to the expression level of CstF-77 as well as several other C/P factors, indicating it attenuates the expression of CstF-77 via a negative feedback mechanism. Significantly, intronic C/P of CstF-77 pre-mRNA correlates with global 3′UTR length across cells and tissues. In addition, inhibition of U1 snRNP also leads to regulation of the usage of In3 pA, suggesting that the C/P activity in the cell can be cross-regulated by splicing, leading to coordination between these two processes. Importantly, perturbation of CstF-77 expression leads to widespread alternative cleavage and polyadenylation (APA) and disturbance of cell proliferation and differentiation. Thus, the conserved intronic pA of the CstF-77 gene may function as a sensor for cellular C/P and splicing activities, controlling the homeostasis of CstF-77 and C/P activity and impacting cell proliferation and differentiation. Public Library of Science 2013-07-11 /pmc/articles/PMC3708835/ /pubmed/23874216 http://dx.doi.org/10.1371/journal.pgen.1003613 Text en © 2013 Luo et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Luo, Wenting
Ji, Zhe
Pan, Zhenhua
You, Bei
Hoque, Mainul
Li, Wencheng
Gunderson, Samuel I.
Tian, Bin
The Conserved Intronic Cleavage and Polyadenylation Site of CstF-77 Gene Imparts Control of 3′ End Processing Activity through Feedback Autoregulation and by U1 snRNP
title The Conserved Intronic Cleavage and Polyadenylation Site of CstF-77 Gene Imparts Control of 3′ End Processing Activity through Feedback Autoregulation and by U1 snRNP
title_full The Conserved Intronic Cleavage and Polyadenylation Site of CstF-77 Gene Imparts Control of 3′ End Processing Activity through Feedback Autoregulation and by U1 snRNP
title_fullStr The Conserved Intronic Cleavage and Polyadenylation Site of CstF-77 Gene Imparts Control of 3′ End Processing Activity through Feedback Autoregulation and by U1 snRNP
title_full_unstemmed The Conserved Intronic Cleavage and Polyadenylation Site of CstF-77 Gene Imparts Control of 3′ End Processing Activity through Feedback Autoregulation and by U1 snRNP
title_short The Conserved Intronic Cleavage and Polyadenylation Site of CstF-77 Gene Imparts Control of 3′ End Processing Activity through Feedback Autoregulation and by U1 snRNP
title_sort conserved intronic cleavage and polyadenylation site of cstf-77 gene imparts control of 3′ end processing activity through feedback autoregulation and by u1 snrnp
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708835/
https://www.ncbi.nlm.nih.gov/pubmed/23874216
http://dx.doi.org/10.1371/journal.pgen.1003613
work_keys_str_mv AT luowenting theconservedintroniccleavageandpolyadenylationsiteofcstf77geneimpartscontrolof3endprocessingactivitythroughfeedbackautoregulationandbyu1snrnp
AT jizhe theconservedintroniccleavageandpolyadenylationsiteofcstf77geneimpartscontrolof3endprocessingactivitythroughfeedbackautoregulationandbyu1snrnp
AT panzhenhua theconservedintroniccleavageandpolyadenylationsiteofcstf77geneimpartscontrolof3endprocessingactivitythroughfeedbackautoregulationandbyu1snrnp
AT youbei theconservedintroniccleavageandpolyadenylationsiteofcstf77geneimpartscontrolof3endprocessingactivitythroughfeedbackautoregulationandbyu1snrnp
AT hoquemainul theconservedintroniccleavageandpolyadenylationsiteofcstf77geneimpartscontrolof3endprocessingactivitythroughfeedbackautoregulationandbyu1snrnp
AT liwencheng theconservedintroniccleavageandpolyadenylationsiteofcstf77geneimpartscontrolof3endprocessingactivitythroughfeedbackautoregulationandbyu1snrnp
AT gundersonsamueli theconservedintroniccleavageandpolyadenylationsiteofcstf77geneimpartscontrolof3endprocessingactivitythroughfeedbackautoregulationandbyu1snrnp
AT tianbin theconservedintroniccleavageandpolyadenylationsiteofcstf77geneimpartscontrolof3endprocessingactivitythroughfeedbackautoregulationandbyu1snrnp
AT luowenting conservedintroniccleavageandpolyadenylationsiteofcstf77geneimpartscontrolof3endprocessingactivitythroughfeedbackautoregulationandbyu1snrnp
AT jizhe conservedintroniccleavageandpolyadenylationsiteofcstf77geneimpartscontrolof3endprocessingactivitythroughfeedbackautoregulationandbyu1snrnp
AT panzhenhua conservedintroniccleavageandpolyadenylationsiteofcstf77geneimpartscontrolof3endprocessingactivitythroughfeedbackautoregulationandbyu1snrnp
AT youbei conservedintroniccleavageandpolyadenylationsiteofcstf77geneimpartscontrolof3endprocessingactivitythroughfeedbackautoregulationandbyu1snrnp
AT hoquemainul conservedintroniccleavageandpolyadenylationsiteofcstf77geneimpartscontrolof3endprocessingactivitythroughfeedbackautoregulationandbyu1snrnp
AT liwencheng conservedintroniccleavageandpolyadenylationsiteofcstf77geneimpartscontrolof3endprocessingactivitythroughfeedbackautoregulationandbyu1snrnp
AT gundersonsamueli conservedintroniccleavageandpolyadenylationsiteofcstf77geneimpartscontrolof3endprocessingactivitythroughfeedbackautoregulationandbyu1snrnp
AT tianbin conservedintroniccleavageandpolyadenylationsiteofcstf77geneimpartscontrolof3endprocessingactivitythroughfeedbackautoregulationandbyu1snrnp