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U1 snRNP proteins promote proximal alternative polyadenylation sites by directly interacting with 3′ end processing core factors

In eukaryotic cells, both alternative splicing and alternative polyadenylation (APA) play essential roles in the gene regulation network. U1 small ribonucleoprotein particle (U1 snRNP) is a major component of spliceosome, and U1 snRNP complex can suppress proximal APA sites through crosstalking with...

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Autores principales: Hu, Zhijie, Li, Mengxia, Huo, Zhanfeng, Chen, Liutao, Liu, Susu, Deng, Ke, Lu, Xin, Chen, Shangwu, Fu, Yonggui, Xu, Anlong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9926334/
https://www.ncbi.nlm.nih.gov/pubmed/36073763
http://dx.doi.org/10.1093/jmcb/mjac054
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author Hu, Zhijie
Li, Mengxia
Huo, Zhanfeng
Chen, Liutao
Liu, Susu
Deng, Ke
Lu, Xin
Chen, Shangwu
Fu, Yonggui
Xu, Anlong
author_facet Hu, Zhijie
Li, Mengxia
Huo, Zhanfeng
Chen, Liutao
Liu, Susu
Deng, Ke
Lu, Xin
Chen, Shangwu
Fu, Yonggui
Xu, Anlong
author_sort Hu, Zhijie
collection PubMed
description In eukaryotic cells, both alternative splicing and alternative polyadenylation (APA) play essential roles in the gene regulation network. U1 small ribonucleoprotein particle (U1 snRNP) is a major component of spliceosome, and U1 snRNP complex can suppress proximal APA sites through crosstalking with 3′ end processing factors. However, here we show that both knockdown and overexpression of SNRPA, SNRPC, SNRNP70, and SNRPD2, the U1 snRNP proteins, promote the usage of proximal APA sites at the transcriptome level. SNRNP70 can drive the phase transition of PABPN1 from droplet to aggregate, which may reduce the repressive effects of PABPN1 on the proximal APA sites. Additionally, SNRNP70 can also promote the proximal APA sites by recruiting CPSF6, suggesting that the function of CPSF6 on APA is related with other RNA-binding proteins and cell context-dependent. Consequently, these results reveal that, on the contrary to U1 snRNP complex, the free proteins of U1 snRNP complex can promote proximal APA sites through the interaction with 3′ end processing machinery.
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spelling pubmed-99263342023-02-14 U1 snRNP proteins promote proximal alternative polyadenylation sites by directly interacting with 3′ end processing core factors Hu, Zhijie Li, Mengxia Huo, Zhanfeng Chen, Liutao Liu, Susu Deng, Ke Lu, Xin Chen, Shangwu Fu, Yonggui Xu, Anlong J Mol Cell Biol Article In eukaryotic cells, both alternative splicing and alternative polyadenylation (APA) play essential roles in the gene regulation network. U1 small ribonucleoprotein particle (U1 snRNP) is a major component of spliceosome, and U1 snRNP complex can suppress proximal APA sites through crosstalking with 3′ end processing factors. However, here we show that both knockdown and overexpression of SNRPA, SNRPC, SNRNP70, and SNRPD2, the U1 snRNP proteins, promote the usage of proximal APA sites at the transcriptome level. SNRNP70 can drive the phase transition of PABPN1 from droplet to aggregate, which may reduce the repressive effects of PABPN1 on the proximal APA sites. Additionally, SNRNP70 can also promote the proximal APA sites by recruiting CPSF6, suggesting that the function of CPSF6 on APA is related with other RNA-binding proteins and cell context-dependent. Consequently, these results reveal that, on the contrary to U1 snRNP complex, the free proteins of U1 snRNP complex can promote proximal APA sites through the interaction with 3′ end processing machinery. Oxford University Press 2022-09-08 /pmc/articles/PMC9926334/ /pubmed/36073763 http://dx.doi.org/10.1093/jmcb/mjac054 Text en © The Author(s) (2022). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, CEMCS, CAS. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Article
Hu, Zhijie
Li, Mengxia
Huo, Zhanfeng
Chen, Liutao
Liu, Susu
Deng, Ke
Lu, Xin
Chen, Shangwu
Fu, Yonggui
Xu, Anlong
U1 snRNP proteins promote proximal alternative polyadenylation sites by directly interacting with 3′ end processing core factors
title U1 snRNP proteins promote proximal alternative polyadenylation sites by directly interacting with 3′ end processing core factors
title_full U1 snRNP proteins promote proximal alternative polyadenylation sites by directly interacting with 3′ end processing core factors
title_fullStr U1 snRNP proteins promote proximal alternative polyadenylation sites by directly interacting with 3′ end processing core factors
title_full_unstemmed U1 snRNP proteins promote proximal alternative polyadenylation sites by directly interacting with 3′ end processing core factors
title_short U1 snRNP proteins promote proximal alternative polyadenylation sites by directly interacting with 3′ end processing core factors
title_sort u1 snrnp proteins promote proximal alternative polyadenylation sites by directly interacting with 3′ end processing core factors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9926334/
https://www.ncbi.nlm.nih.gov/pubmed/36073763
http://dx.doi.org/10.1093/jmcb/mjac054
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