Biogenesis of C. elegans spermatogenesis small RNAs is initiated by a zc3h12a-like ribonuclease

Sci Adv. 2022 Aug 12;8(32):eabm0699. doi: 10.1126/sciadv.abm0699. Epub 2022 Aug 10.


Small RNAs regulate spermatogenesis across species ranging from Caenorhabditis elegans to humans. In C. elegans, two Argonaute proteins, ALG-3 and ALG-4, and their associated alg-3/4 26G-small RNAs are essential for spermiogenesis at 25°C. The alg-3/4 26G-small RNAs are antisense to their target mRNAs and produced by the RNA-dependent RNA polymerase, RRF-3. However, it remains unclear how the RNA templates for RRF-3 are generated and which cellular processes are affected by alg-3/4 26G-small RNAs. Here, we demonstrate a previously unidentified zc3h12a-like ribonuclease protein, NYN-3, in alg-3/4 26G-small RNAs biogenesis. NYN-3 is not only required for proper abundance of alg-3/4 26G-small RNAs but also crosslinked to their targeted mRNAs before RRF-3 from ePAR-CLIP-seq. Bioinformatics analysis was then used to parse the 26G-small RNA-targeted genes into functional subclasses. Collectively, these findings implicate NYN-3 as an initiator of alg-3/4 26G-small RNA generation.

MeSH terms

  • Animals
  • Caenorhabditis elegans Proteins* / genetics
  • Caenorhabditis elegans Proteins* / metabolism
  • Caenorhabditis elegans* / genetics
  • Caenorhabditis elegans* / metabolism
  • Endoribonucleases / metabolism
  • Humans
  • Male
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Ribonucleases / metabolism
  • Spermatogenesis / genetics
  • Transcription Factors / metabolism


  • Caenorhabditis elegans Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Transcription Factors
  • Endoribonucleases
  • Ribonucleases
  • ZC3H12A protein, human