Cargando…

Son maintains accurate splicing for a subset of human pre-mRNAs

Serine-arginine-rich (SR) proteins play a key role in alternative pre-mRNA splicing in eukaryotes. We recently showed that a large SR protein called Son has unique repeat motifs that are essential for maintaining the subnuclear organization of pre-mRNA processing factors in nuclear speckles. Motif a...

Descripción completa

Detalles Bibliográficos
Autores principales: Sharma, Alok, Markey, Michael, Torres-Muñoz, Keshia, Varia, Sapna, Kadakia, Madhavi, Bubulya, Athanasios, Bubulya, Paula A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Company of Biologists 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3258111/
https://www.ncbi.nlm.nih.gov/pubmed/22193954
http://dx.doi.org/10.1242/jcs.092239
_version_ 1782221228499533824
author Sharma, Alok
Markey, Michael
Torres-Muñoz, Keshia
Varia, Sapna
Kadakia, Madhavi
Bubulya, Athanasios
Bubulya, Paula A.
author_facet Sharma, Alok
Markey, Michael
Torres-Muñoz, Keshia
Varia, Sapna
Kadakia, Madhavi
Bubulya, Athanasios
Bubulya, Paula A.
author_sort Sharma, Alok
collection PubMed
description Serine-arginine-rich (SR) proteins play a key role in alternative pre-mRNA splicing in eukaryotes. We recently showed that a large SR protein called Son has unique repeat motifs that are essential for maintaining the subnuclear organization of pre-mRNA processing factors in nuclear speckles. Motif analysis of Son highlights putative RNA interaction domains that suggest a direct role for Son in pre-mRNA splicing. Here, we used in situ approaches to show that Son localizes to a reporter minigene transcription site, and that RNAi-mediated Son depletion causes exon skipping on reporter transcripts at this transcription site. A genome-wide exon microarray analysis was performed to identify human transcription and splicing targets of Son. Our data show that Son-regulated splicing encompasses all known types of alternative splicing, the most common being alternative splicing of cassette exons. We confirmed that knockdown of Son leads to exon skipping in pre-mRNAs for chromatin-modifying enzymes, including ADA, HDAC6 and SetD8. This study reports a comprehensive view of human transcription and splicing targets for Son in fundamental cellular pathways such as integrin-mediated cell adhesion, cell cycle regulation, cholesterol biosynthesis, apoptosis and epigenetic regulation of gene expression.
format Online
Article
Text
id pubmed-3258111
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher Company of Biologists
record_format MEDLINE/PubMed
spelling pubmed-32581112012-01-19 Son maintains accurate splicing for a subset of human pre-mRNAs Sharma, Alok Markey, Michael Torres-Muñoz, Keshia Varia, Sapna Kadakia, Madhavi Bubulya, Athanasios Bubulya, Paula A. J Cell Sci Research Articles Serine-arginine-rich (SR) proteins play a key role in alternative pre-mRNA splicing in eukaryotes. We recently showed that a large SR protein called Son has unique repeat motifs that are essential for maintaining the subnuclear organization of pre-mRNA processing factors in nuclear speckles. Motif analysis of Son highlights putative RNA interaction domains that suggest a direct role for Son in pre-mRNA splicing. Here, we used in situ approaches to show that Son localizes to a reporter minigene transcription site, and that RNAi-mediated Son depletion causes exon skipping on reporter transcripts at this transcription site. A genome-wide exon microarray analysis was performed to identify human transcription and splicing targets of Son. Our data show that Son-regulated splicing encompasses all known types of alternative splicing, the most common being alternative splicing of cassette exons. We confirmed that knockdown of Son leads to exon skipping in pre-mRNAs for chromatin-modifying enzymes, including ADA, HDAC6 and SetD8. This study reports a comprehensive view of human transcription and splicing targets for Son in fundamental cellular pathways such as integrin-mediated cell adhesion, cell cycle regulation, cholesterol biosynthesis, apoptosis and epigenetic regulation of gene expression. Company of Biologists 2011-12-15 /pmc/articles/PMC3258111/ /pubmed/22193954 http://dx.doi.org/10.1242/jcs.092239 Text en © 2011. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License, which permits unrestricted non-commercial use, distribution and reproduction in any medium provided that the original work is properly cited and all further distributions of the work or adaptation are subject to the same Creative Commons License terms.
spellingShingle Research Articles
Sharma, Alok
Markey, Michael
Torres-Muñoz, Keshia
Varia, Sapna
Kadakia, Madhavi
Bubulya, Athanasios
Bubulya, Paula A.
Son maintains accurate splicing for a subset of human pre-mRNAs
title Son maintains accurate splicing for a subset of human pre-mRNAs
title_full Son maintains accurate splicing for a subset of human pre-mRNAs
title_fullStr Son maintains accurate splicing for a subset of human pre-mRNAs
title_full_unstemmed Son maintains accurate splicing for a subset of human pre-mRNAs
title_short Son maintains accurate splicing for a subset of human pre-mRNAs
title_sort son maintains accurate splicing for a subset of human pre-mrnas
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3258111/
https://www.ncbi.nlm.nih.gov/pubmed/22193954
http://dx.doi.org/10.1242/jcs.092239
work_keys_str_mv AT sharmaalok sonmaintainsaccuratesplicingforasubsetofhumanpremrnas
AT markeymichael sonmaintainsaccuratesplicingforasubsetofhumanpremrnas
AT torresmunozkeshia sonmaintainsaccuratesplicingforasubsetofhumanpremrnas
AT variasapna sonmaintainsaccuratesplicingforasubsetofhumanpremrnas
AT kadakiamadhavi sonmaintainsaccuratesplicingforasubsetofhumanpremrnas
AT bubulyaathanasios sonmaintainsaccuratesplicingforasubsetofhumanpremrnas
AT bubulyapaulaa sonmaintainsaccuratesplicingforasubsetofhumanpremrnas