Angulin proteins ILDR1 and ILDR2 regulate alternative pre-mRNA splicing through binding to splicing factors TRA2A, TRA2B, or SRSF1

Abstract Angulin proteins are a group of evolutionally conserved type I transmembrane proteins that contain an extracellular Ig-like domain. In mammals, three angulin proteins have been identified, namely immunoglobulin-like domain containing receptor 1 (ILDR1), immunoglobulin-like domain containing...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Yueyue Liu, Hongyun Nie, Chengcheng Liu, Xiaoyan Zhai, Qing Sang, Yanfei Wang, Deli Shi, Lei Wang, Zhigang Xu
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2017
Materias:
R
Q
Acceso en línea:https://doaj.org/article/5aed33fc11de4b65a648c2c042a57c27
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:5aed33fc11de4b65a648c2c042a57c27
record_format dspace
spelling oai:doaj.org-article:5aed33fc11de4b65a648c2c042a57c272021-12-02T12:31:53ZAngulin proteins ILDR1 and ILDR2 regulate alternative pre-mRNA splicing through binding to splicing factors TRA2A, TRA2B, or SRSF110.1038/s41598-017-07530-z2045-2322https://doaj.org/article/5aed33fc11de4b65a648c2c042a57c272017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07530-zhttps://doaj.org/toc/2045-2322Abstract Angulin proteins are a group of evolutionally conserved type I transmembrane proteins that contain an extracellular Ig-like domain. In mammals, three angulin proteins have been identified, namely immunoglobulin-like domain containing receptor 1 (ILDR1), immunoglobulin-like domain containing receptor 2 (ILDR2), and lipolysis-stimulated lipoprotein receptor (LSR). All three proteins have been shown to localize at tight junctions (TJs) and are important for TJ formation. Mutations in ILDR1 gene have been shown to cause non-syndromic hearing loss (NSHL). In the present work, we show that ILDR1 binds to splicing factors TRA2A, TRA2B, and SRSF1, and translocates into the nuclei when the splicing factors are present. Moreover, ILDR1 affects alternative splicing of Tubulin delta 1 (TUBD1), IQ motif containing B1 (IQCB1), and Protocadherin 19 (Pcdh19). Further investigation show that ILDR2, but not LSR, also binds to the splicing factors and regulates alternative splicing. When endogenous ILDR1 and ILDR2 expression is knockdown with siRNAs in cultured cells, alternative splicing of TUBD1 and IQCB1 is affected. In conclusion, we show here that angulin proteins ILDR1 and ILDR2 are involved in alternative pre-mRNA splicing via binding to splicing factors TRA2A, TRA2B, or SRSF1.Yueyue LiuHongyun NieChengcheng LiuXiaoyan ZhaiQing SangYanfei WangDeli ShiLei WangZhigang XuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yueyue Liu
Hongyun Nie
Chengcheng Liu
Xiaoyan Zhai
Qing Sang
Yanfei Wang
Deli Shi
Lei Wang
Zhigang Xu
Angulin proteins ILDR1 and ILDR2 regulate alternative pre-mRNA splicing through binding to splicing factors TRA2A, TRA2B, or SRSF1
description Abstract Angulin proteins are a group of evolutionally conserved type I transmembrane proteins that contain an extracellular Ig-like domain. In mammals, three angulin proteins have been identified, namely immunoglobulin-like domain containing receptor 1 (ILDR1), immunoglobulin-like domain containing receptor 2 (ILDR2), and lipolysis-stimulated lipoprotein receptor (LSR). All three proteins have been shown to localize at tight junctions (TJs) and are important for TJ formation. Mutations in ILDR1 gene have been shown to cause non-syndromic hearing loss (NSHL). In the present work, we show that ILDR1 binds to splicing factors TRA2A, TRA2B, and SRSF1, and translocates into the nuclei when the splicing factors are present. Moreover, ILDR1 affects alternative splicing of Tubulin delta 1 (TUBD1), IQ motif containing B1 (IQCB1), and Protocadherin 19 (Pcdh19). Further investigation show that ILDR2, but not LSR, also binds to the splicing factors and regulates alternative splicing. When endogenous ILDR1 and ILDR2 expression is knockdown with siRNAs in cultured cells, alternative splicing of TUBD1 and IQCB1 is affected. In conclusion, we show here that angulin proteins ILDR1 and ILDR2 are involved in alternative pre-mRNA splicing via binding to splicing factors TRA2A, TRA2B, or SRSF1.
format article
author Yueyue Liu
Hongyun Nie
Chengcheng Liu
Xiaoyan Zhai
Qing Sang
Yanfei Wang
Deli Shi
Lei Wang
Zhigang Xu
author_facet Yueyue Liu
Hongyun Nie
Chengcheng Liu
Xiaoyan Zhai
Qing Sang
Yanfei Wang
Deli Shi
Lei Wang
Zhigang Xu
author_sort Yueyue Liu
title Angulin proteins ILDR1 and ILDR2 regulate alternative pre-mRNA splicing through binding to splicing factors TRA2A, TRA2B, or SRSF1
title_short Angulin proteins ILDR1 and ILDR2 regulate alternative pre-mRNA splicing through binding to splicing factors TRA2A, TRA2B, or SRSF1
title_full Angulin proteins ILDR1 and ILDR2 regulate alternative pre-mRNA splicing through binding to splicing factors TRA2A, TRA2B, or SRSF1
title_fullStr Angulin proteins ILDR1 and ILDR2 regulate alternative pre-mRNA splicing through binding to splicing factors TRA2A, TRA2B, or SRSF1
title_full_unstemmed Angulin proteins ILDR1 and ILDR2 regulate alternative pre-mRNA splicing through binding to splicing factors TRA2A, TRA2B, or SRSF1
title_sort angulin proteins ildr1 and ildr2 regulate alternative pre-mrna splicing through binding to splicing factors tra2a, tra2b, or srsf1
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/5aed33fc11de4b65a648c2c042a57c27
work_keys_str_mv AT yueyueliu angulinproteinsildr1andildr2regulatealternativepremrnasplicingthroughbindingtosplicingfactorstra2atra2borsrsf1
AT hongyunnie angulinproteinsildr1andildr2regulatealternativepremrnasplicingthroughbindingtosplicingfactorstra2atra2borsrsf1
AT chengchengliu angulinproteinsildr1andildr2regulatealternativepremrnasplicingthroughbindingtosplicingfactorstra2atra2borsrsf1
AT xiaoyanzhai angulinproteinsildr1andildr2regulatealternativepremrnasplicingthroughbindingtosplicingfactorstra2atra2borsrsf1
AT qingsang angulinproteinsildr1andildr2regulatealternativepremrnasplicingthroughbindingtosplicingfactorstra2atra2borsrsf1
AT yanfeiwang angulinproteinsildr1andildr2regulatealternativepremrnasplicingthroughbindingtosplicingfactorstra2atra2borsrsf1
AT delishi angulinproteinsildr1andildr2regulatealternativepremrnasplicingthroughbindingtosplicingfactorstra2atra2borsrsf1
AT leiwang angulinproteinsildr1andildr2regulatealternativepremrnasplicingthroughbindingtosplicingfactorstra2atra2borsrsf1
AT zhigangxu angulinproteinsildr1andildr2regulatealternativepremrnasplicingthroughbindingtosplicingfactorstra2atra2borsrsf1
_version_ 1718394215714521088