Welcome to the UPF Digital Repository

Impaired spermatogenesis, muscle, and erythrocyte function in U12 intron splicing-defective Zrsr1 mutant mice

Show simple item record

dc.contributor.author Horiuchi, Keiko
dc.contributor.author Papasaikas, Panagiotis
dc.contributor.author Valcárcel, J. (Juan)
dc.contributor.author Gutiérrez-Adán, Alfonso
dc.date.accessioned 2019-11-04T08:47:53Z
dc.date.available 2019-11-04T08:47:53Z
dc.date.issued 2018
dc.identifier.citation Horiuchi K, Perez-Cerezales S, Papasaikas P, Ramos-Ibeas P, López-Cardona AP, Laguna-Barraza R et al. Impaired spermatogenesis, muscle, and erythrocyte function in U12 intron splicing-defective Zrsr1 mutant mice. Cell Rep. 2018; 23(1):143-155. DOI 10.1016/j.celrep.2018.03.028
dc.identifier.issn 2211-1247
dc.identifier.uri http://hdl.handle.net/10230/42589
dc.description.abstract The U2AF35-like ZRSR1 has been implicated in the recognition of 3' splice site during spliceosome assembly, but ZRSR1 knockout mice do not show abnormal phenotypes. To analyze ZRSR1 function and its precise role in RNA splicing, we generated ZRSR1 mutant mice containing truncating mutations within its RNA-recognition motif. Homozygous mutant mice exhibited severe defects in erythrocytes, muscle stretch, and spermatogenesis, along with germ cell sloughing and apoptosis, ultimately leading to azoospermia and male sterility. Testis RNA sequencing (RNA-seq) analyses revealed increased intron retention of both U2- and U12-type introns, including U12-type intron events in genes with key functions in spermatogenesis and spermatid development. Affected U2 introns were commonly found flanking U12 introns, suggesting functional cross-talk between the two spliceosomes. The splicing and tissue defects observed in mutant mice attributed to ZRSR1 loss of function suggest a physiological role for this factor in U12 intron splicing.
dc.description.sponsorship This work was funded by grants AGL2012-39652, BFU2014-55058-P, and AGL2015-66145 from the Spanish Ministry of Economy and Competitiveness and Japan Grants-in-Aid for Scientific Research 26830124 from the Ministry of Education, Culture, Sports, Science and Technology. K.H. was supported by Young Scientists Development Program, Research Center for Advanced Science and Technology at the University of Tokyo (funded by FUJIFILM Corporation). Work in J.V.'s lab was also supported by the European Research Council (ERC AdG - GA670146 - MASCP).
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Cell Rep. 2018; 23(1):143-155
dc.rights © 2018 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.title Impaired spermatogenesis, muscle, and erythrocyte function in U12 intron splicing-defective Zrsr1 mutant mice
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2018.03.028
dc.subject.keyword Zrsr1 mutant mice
dc.subject.keyword RNA splicing
dc.subject.keyword Spermatogenesis defects
dc.subject.keyword Minor introns
dc.subject.keyword Intron retention
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/AGL2012-39652
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-55058-P
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/AGL2015-66145
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


This item appears in the following Collection(s)

Show simple item record

Search DSpace


Advanced Search

Browse

My Account

Statistics

Compliant to Partaking