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

The U2AF35-like ZRSR1 has been implicated in the recognition of 30 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 (RNAseq) 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 crosstalk 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.

Bibliographic Details

Main Authors:	Horiuchi, K., Pérez Cerezales, Serafín, Papasaikas, P., Ramos Ibeas, Priscila, López-Cardona, A. P., Laguna-Barraza, R., Fonseca Balvís, N., Pericuesta Camacho, Eva, Fernández González, Raúl, Planells, B., Viera, A., Suja, J. A., Ross, P. J., Alén, F., Orio, L., Rodriguez de Fonseca, F., Pintado, B., Valcárcel, J., Gutiérrez Adán, Alfonso
Format:	artículo biblioteca
Language:	English
Published:	Cell Press 2018
Subjects:	Zrsr1 mutant mice, RNA splicing, Spermatogenesis defects, Minor introns, Intron retention,
Online Access:	http://hdl.handle.net/20.500.12792/583 http://hdl.handle.net/10261/290641
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