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m6A-dependent biogenesis of circular RNAs in male germ cells
- Source :
- Cell Research. 30:211-228
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- The majority of circular RNAs (circRNAs) spliced from coding genes contain open reading frames (ORFs) and thus, have protein coding potential. However, it remains unknown what regulates the biogenesis of these ORF-containing circRNAs, whether they are actually translated into proteins and what functions they play in specific physiological contexts. Here, we report that a large number of circRNAs are synthesized with increasing abundance when late pachytene spermatocytes develop into round and then elongating spermatids during murine spermatogenesis. For a subset of circRNAs, the back splicing appears to occur mostly at m6A-enriched sites, which are usually located around the start and stop codons in linear mRNAs. Consequently, approximately a half of these male germ cell circRNAs contain large ORFs with m6A-modified start codons in their junctions, features that have been recently shown to be associated with protein-coding potential. Hundreds of peptides encoded by the junction sequences of these circRNAs were detected using liquid chromatography coupled with mass spectrometry, suggesting that these circRNAs can indeed be translated into proteins in both developing (spermatocytes and spermatids) and mature (spermatozoa) male germ cells. The present study discovered not only a novel role of m6A in the biogenesis of coding circRNAs, but also a potential mechanism to ensure stable and long-lasting protein production in the absence of linear mRNAs, i.e., through production of circRNAs containing large ORFs and m6A-modified start codons in junction sequences.
- Subjects :
- 0303 health sciences
Cell Biology
Biology
Stop codon
Cell biology
03 medical and health sciences
Open reading frame
0302 clinical medicine
medicine.anatomical_structure
Start codon
medicine
Protein biosynthesis
ORFS
Molecular Biology
Gene
030217 neurology & neurosurgery
Biogenesis
Germ cell
030304 developmental biology
Subjects
Details
- ISSN :
- 17487838 and 10010602
- Volume :
- 30
- Database :
- OpenAIRE
- Journal :
- Cell Research
- Accession number :
- edsair.doi...........002c0cf8684f8ceee30325c59dddfa63