The mouse Sry locus harbors a cryptic exon that is essential for male sex determination

Abstract

The mammalian sex-determining gene Sry induces male development. Since its discovery 30 years ago, Sry has been believed to be a single-exon gene. Here, we identified a cryptic second exon of mouse Sry and a corresponding two-exon type Sry (Sry-T) transcript. XY mice lacking Sry-T were sex-reversed, and ectopic expression of Sry-T in XX mice induced male development. Sry-T messenger RNA is expressed similarly to that of canonical single-exon type Sry (Sry-S), but SRY-T protein is expressed predominantly because of the absence of a degron in the C terminus of SRY-S. Sry exon2 appears to have evolved recently in mice through acquisition of a retrotransposon-derived coding sequence to replace the degron. Our findings suggest that in nature, SRY-T, not SRY-S, is the bona fide testis-determining factor.

Origin, specification and differentiation of a rare supporting-like lineage in the developing mouse gonad

“…Data were mapped to the mouse reference genome GRCm38.p5 in which the eGFP (NC_011521.1) combined with the bovine GH 3’-splice/polyadenylation signals ( 39 ) (NM_180996.1) sequences have been added. It has recently been established that the mouse Sry locus harbors a cryptic exon that is essential for male sex determination ( 63 ). As this exon is located in a palindromic region, all reads mapping to this region are also mapping to the positive strand and discarded as multimappers.…”

NANOS2 suppresses the cell cycle by repressing mTORC1 activators in embryonic male germ cells

“…Unfortunately, Sry itself was not called in our scRNA-seq data. Recently, however, it was reported that Sry has an additional exon downstream of the classical exon ( Miyawaki et al., 2020 ). Indeed, our scRNA-seq detected many reads from exon 2 ( Figure S6 A).…”

A brief review of vertebrate sex evolution with a pledge for integrative research: towards ‘sexomics’

“…The gene regulatory network of male and female SD- and developmental pathways are best-studied in laboratory house mice [ 7 ]. While for 30 years Sry has been thought to comprise a single exon, a cryptic second exon, essential for male SD in mice has just been identified [ 337 ]. Although eutherian XX/XY sex determination is extremely conserved, a few rodent species evolved unusual, derived sex chromosome systems [ 338 ].…”