The m6A reader PRRC2A is essential for meiosis I completion during spermatogenesis

Abstract

N6-methyladenosine (m6A) and its reader proteins YTHDC1, YTHDC2, and YTHDF2 have been shown to exert essential functions during spermatogenesis. However, much remains unknown about m6A regulation mechanisms and the functions of specific readers during the meiotic cell cycle. Here, we show that the m6A reader Proline rich coiled-coil 2A (PRRC2A) is essential for male fertility. Germ cell-specific knockout of Prrc2a causes XY asynapsis and impaired meiotic sex chromosome inactivation in late-prophase spermatocytes. Moreover, PRRC2A-null spermatocytes exhibit delayed metaphase entry, chromosome misalignment, and spindle disorganization at metaphase I and are finally arrested at this stage. Sequencing data reveal that PRRC2A decreases the RNA abundance or improves the translation efficiency of targeting transcripts. Specifically, PRRC2A recognizes spermatogonia-specific transcripts and downregulates their RNA abundance to maintain the spermatocyte expression pattern during the meiosis prophase. For genes involved in meiotic cell division, PRRC2A improves the translation efficiency of their transcripts. Further, co-immunoprecipitation data show that PRRC2A interacts with several proteins regulating mRNA metabolism or translation (YBX1, YBX2, PABPC1, FXR1, and EIF4G3). Our study reveals post-transcriptional functions of PRRC2A and demonstrates its critical role in the completion of meiosis I in spermatogenesis.

Comparative Analysis of Differential Cellular Transcriptome and Proteome Regulation by HIV-1 and HIV-2 Pseudovirions in the Early Phase of Infection

“…In contrast to HIV-1, HIV-2 downregulated NCAPH and PRRC2A, two proteins that are known to play an important role in cell proliferation and migration [ 77 , 78 ]. Retroviruses and, indeed, DNA and RNA viruses, in general, are known to modulate the cell cycle and cellular proliferation in order to facilitate viral replication and survival [ 79 ].…”

RNA m6A modification, signals for degradation or stabilisation?

“…PRRC2A stabilises Olig2 mRNAs by binding to the m 6 A within the coding sequence region of Olig2 and this stabilisation effect is reversible through the action of the m 6 A demethylase FTO. However, another recent study showed that PRRC2A recognises spermatogonia-specific transcripts and down-regulate their RNA abundance [ 68 ], thereby maintaining the spermatocyte expression pattern during the meiosis prophase. It is important to note that this analysis was conducted on a transcriptome-wide scale rather than focusing on individual transcripts.…”

The regulatory role of m6A modification in the maintenance and differentiation of embryonic stem cells

“… 56 Expectedly, more m 6 A-binding proteins are identified to expand the reservoir of m 6 A readers for executing different post-transcriptional regulation of RNAs, such as heterogeneous nuclear ribonucleoprotein (HNRNP) family, 57 fragile X mental-retardation protein (FMR1), 58 , 59 and proline-rich coiled-coil 2A. 60 , 61 …”