An ancient germ cell-specific RNA-binding protein protects the germline from cryptic splice site poisoning.
Ingrid EhrmannJames H CrichtonMatthew R GazzaraKatherine JamesYilei LiuSushma Nagaraja GrellscheidTomaz CurkDirk G de RooijJannetta S SteynSimon CockellIan R AdamsYoseph BarashDavid J ElliottPublished in: eLife (2019)
Male germ cells of all placental mammals express an ancient nuclear RNA binding protein of unknown function called RBMXL2. Here we find that deletion of the retrogene encoding RBMXL2 blocks spermatogenesis. Transcriptome analyses of age-matched deletion mice show that RBMXL2 controls splicing patterns during meiosis. In particular, RBMXL2 represses the selection of aberrant splice sites and the insertion of cryptic and premature terminal exons. Our data suggest a Rbmxl2 retrogene has been conserved across mammals as part of a splicing control mechanism that is fundamentally important to germ cell biology. We propose that this mechanism is essential to meiosis because it buffers the high ambient concentrations of splicing activators, thereby preventing poisoning of key transcripts and disruption to gene expression by aberrant splice site selection.
Keyphrases
- germ cell
- binding protein
- gene expression
- induced apoptosis
- dna methylation
- air pollution
- cell cycle arrest
- dna repair
- transcription factor
- electronic health record
- rna seq
- genome wide
- endoplasmic reticulum stress
- type diabetes
- oxidative stress
- big data
- cell proliferation
- adipose tissue
- insulin resistance
- skeletal muscle
- signaling pathway
- artificial intelligence
- wild type