Y chromosomal noncoding RNAs regulate autosomal gene expression via piRNAs in mouse testis

Area of Science:

• Genetics
• Reproductive Biology
• Molecular Biology

Background:

• The function of Y chromosome repeats, particularly noncoding transcripts, remains largely unknown.
• Spermatogenesis involves autosomal genes, but Y chromosome long arm (Yq) deletions cause male infertility, suggesting Yq's role.
• This study investigates novel noncoding RNAs from mouse Yq and their potential link to autosomal gene regulation in the testis.

Purpose of the Study:

• To identify and characterize novel long noncoding RNAs (lncRNAs) originating from the mouse male-specific Y long arm (MSYq).
• To explore the relationship between these MSYq-derived lncRNAs and autosomal genes involved in spermatogenesis.
• To investigate the potential role of these ncRNAs and associated piRNAs in male fertility and speciation.

Main Methods:

• Identification and characterization of novel MSYq-derived long noncoding transcripts (Pirmy and Pirmy-like RNAs).
• Analysis of splice variants and copy number variations of these RNAs.
• Differential expression analysis of autosomal sperm proteins in Yq-deleted mutant mice (XY^RIIIqdel).
• Investigation of sequence homology between MSYq RNAs and autosomal genes, identifying piRNA precursors.
• In vitro functional assays to assess piRNA regulatory roles.

Main Results:

• Discovery of novel MSYq-derived lncRNAs, Pirmy and Pirmy-like RNAs, with extensive splice variants and multiple genomic loci.
• Identification of eight differentially expressed autosomal sperm proteins in Yq-deleted mice.
• Demonstration that Pirmy and Pirmy-like RNAs serve as templates for piRNAs, showing homology to 5'/3' UTRs of deregulated autosomal genes.
• In vitro evidence suggests these piRNAs regulate autosomal gene expression.

Conclusions:

• MSYq-derived piRNAs potentially regulate specific autosomal genes in mouse testis.
• Observed sperm phenotypes in Yq-deleted mice resemble those in inter-specific male-sterile hybrids.
• The study provides new understanding of MSYq-derived ncRNAs' roles in male sterility and the process of speciation.