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Published on: February 6, 2018
RBM46 is essential for gametogenesis and functions in post-transcriptional roles affecting meiotic cohesin subunits
Yue Lv1,2,3,4, Gang Lu3, Yuling Cai2,4
1Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250012, China.
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 leptotene and zygotene stage gametes. We found that RBM46 preferentially binds target mRNAs containing GCCUAU/GUUCGA motifs in their 3'UTRs regions. In Rbm46 knockout mice, the RBM46-target cohesin subunits displayed unaltered mRNA levels but had reduced translation, resulting in the failed assembly of axial elements, synapsis disruption, and meiotic arrest. Our study thus provides mechanistic insights into the molecular functions of RBM46 in gametogenesis and illustrates the power of LACE-seq for investigations of RNA-binding protein functions when working with low-abundance input materials.
Insights
RNA-binding protein 46 (RBM46) is crucial for gametogenesis. This study reveals RBM46 regulates meiotic cohesin subunit translation, impacting synaptonemal complex formation and preventing meiotic arrest.
Area of Science:
- Molecular Biology
- Genetics
- Reproductive Biology
Background:
- RNA-binding protein 46 (RBM46) is essential for gametogenesis but its targets and functions are unknown.
- Understanding RBM46's role is critical for deciphering mechanisms of germ cell development.
Purpose of the Study:
- To identify RBM46 targets and elucidate its molecular functions in gametogenesis.
- To investigate the impact of RBM46 on meiotic processes.
Main Methods:
- Utilized LACE-seq (Low-input細胞RNA 結合タンパク質標的配列決定法) for high-resolution RBM46 target profiling in early-stage gametes.
- Employed Rbm46 knockout mouse models to assess in vivo functions.
Main Results:
- RBM46 binds to specific motifs (GCCUAU/GUUCGA) in the 3'UTRs of mRNAs encoding meiotic cohesin subunits.
- RBM46 deficiency leads to reduced translation of target cohesin subunits, impaired synaptonemal complex formation, and meiotic arrest.
- LACE-seq demonstrated effectiveness for low-input samples.
Conclusions:
- RBM46 plays a critical role in gametogenesis by regulating the translation of key meiotic cohesin subunits.
- Disruption of RBM46 function leads to meiotic failure, highlighting its importance in reproductive health.
- LACE-seq is a powerful tool for studying RNA-binding protein targets in limited cell populations.
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