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The RNA-binding protein RBM46 is essential for gametogenesis and functions in post-transcriptional roles affecting meiotic cohesin subunits

ABSTRACT: RBM46 is a germ cell-specific RNA binding protein required for gametogenesis, but the targets and molecular functions of RBM46 remain unknown. Here, we demonstrate that RBM46 binds at specific motifs in the 3'UTRs of mRNAs encoding multiple meiotic cohesin subunits and show that RBM46 is required for normal synaptonemal complex formation during meiosis initiation. Using a recently reported, high-resolution technique known as LACE-seq and working with low-input cells, we profiled the targets of RBM46 at single-nucleotide resolution in gametes of specific meiotic stages leptotene and zygotene. We found that RBM46 preferentially binds target mRNAs containing GCCUAU/GUUCGA motifs in the 3 'UTRs region. In Rbm46 knock-out mice, the RBM46-target cohesin subunits displayed unaltered mRNA levels but had reduced translation, resulting in failed assembly of axial elements, synapsis disruption, and meiotic arrest. Overall, our study provides mechanistic insights into the molecular functions of RBM46 in gametogenesis and illustrates how the power of LACE-seq in the study of RBP functions using low-input materials.

ORGANISM(S): Mus musculus

PROVIDER: GSE201190 | GEO | 2022/04/23

REPOSITORIES: GEO

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