An ancient testis-specific IQ motif-containing H gene regulates specific transcript isoform expression during spermatogenesis

Spermatogenic cells express more alternatively spliced RNAs than most whole tissues; however, the regulation of these events remains unclear. Here, we have characterized the function of a testis-specific IQ motif-containing H gene (Iqch) using a mutant mouse model. We found that Iqch is essential fo...

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Detalles Bibliográficos
Autores: Navarrete-López, Paula, Lombó, Marta, Maroto, Maria, Pericuesta, Eva, Fernández-González, Raúl, Ramos-Ibeas, Priscila, Parra Catalán, María Teresa, Viera Vicario, Alberto, Suja Sánchez, José Ángel, Gutiérrez-Adán, Alfonso
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/708475
Acceso en línea:http://hdl.handle.net/10486/708475
https://dx.doi.org/10.1242/dev.201334
Access Level:acceso abierto
Palabra clave:Iqch
lncRNAs
Spermatogenesis
Biología
Splicing Regulation
Transcript Variants
Biología y Biomedicina / Biología
Descripción
Sumario:Spermatogenic cells express more alternatively spliced RNAs than most whole tissues; however, the regulation of these events remains unclear. Here, we have characterized the function of a testis-specific IQ motif-containing H gene (Iqch) using a mutant mouse model. We found that Iqch is essential for the specific expression of RNA isoforms during spermatogenesis. Using immunohistochemistry of the testis, we noted that Iqch was expressed mainly in the nucleus of spermatocyte and spermatid, where IQCH appeared juxtaposed with SRRM2 and ERSP1 in the nuclear speckles, suggesting that interactions among these proteins regulate alternative splicing (AS). Using RNA-seq, we found that mutant Iqch produces alterations in gene expression, including the clear downregulation of testis-specific lncRNAs and protein-coding genes at the spermatid stage, and AS modifications – principally increased intron retention – resulting in complete male infertility. Interestingly, we identified previously unreported spliced transcripts in the wild-type testis, while mutant Iqch modified the expression and use of hundreds of RNA isoforms, favouring the expression of the canonical form. This suggests that Iqch is part of a splicing control mechanism, which is essential in germ cell biology