Abstract
A non-canonical PRC1 (PRC1.6) prevents precocious meiotic onset. Germ cells alleviate its negative effect by reducing their amount of MAX, a component of PRC1.6, as a prerequisite for their bona fide meiosis. Here, we found that germ cells produced Mga variant mRNA bearing a premature termination codon (PTC) during meiosis as an additional mechanism to impede the function of PRC1.6. The variant mRNA encodes an anomalous MGA protein that lacks the bHLHZ domain and thus functions as a dominant negative regulator of PRC1.6. Notwithstanding the presence of PTC, the Mga variant mRNA are rather stably present in spermatocytes and spermatids due to their intrinsic inefficient background of nonsense-mediated mRNA decay. Thus, our data indicate that meiosis is controlled in a multi-layered manner in which both MAX and MGA, which constitute the core of PRC1.6, are at least used as targets to deteriorate the integrity of the complex to ensure progression of meiosis.
Highlights
Meiosis is a specialized type of cell division, which converts a cell from diploid to haploid[1]
We explored the possibility of an additional molecular mechanism that inactivates the function of polycomb repressive complex 1 (PRC1).6 to ensure meiosis
In accordance with this notion, we have previously demonstrated that protein levels of MAX, which constitutes the core of PRC1.6 with MGA, decrease significantly prior to the onset of meiosis in germ c ells[21]
Summary
Meiosis is a specialized type of cell division, which converts a cell from diploid to haploid[1]. In addition to known exons, SpliceAI indicated a set of high scores for the splice acceptor and donor within the regions of the 15th and 18th introns of the Mga gene marked with blue and red asterisks, respectively. The latter region is enlarged to provide actual scores from SpliceAI. The variant mRNA generated by alternative splicing encodes a carboxy-terminally truncated MGA protein that functions as a dominant negative regulator of PRC1.6 owing to the lack of the basic helix-loop-helix/leucine zipper (bHLHZ) domain. Our data demonstrated that this salient expression profile of Mga variant mRNA represented the combined consequence of preferential production of the variant mRNA in germ cells including spermatogonia and inefficient background of PTC-dependent nonsense-mediated mRNA decay (NMD) in specific subpopulations of germ cells, i.e., meiotic germ cells and spermatids
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