M6A methylation inhibits recruitment of the Dand5 3’UTR to the left-right determinant Bicc1
- 1 Ecole Polytechnique Federale de Lausanne (EPFL), SV ISREC;
- 2 University of Geneva, Department of Molecular Biology
- ↵* Corresponding author; email: daniel.constam{at}epfl.ch
Abstract
In vertebrates, left-right (LR) asymmetry is specified by asymmetric decay of Dand5 messenger RNA (mRNA) mediated by the recruitment of the BicC family RNA binding protein 1 (Bicc1). Besides regulating organ laterality, Bicc1 is required to prevent cystic dilations in renal tubules and in pancreatic and bile ducts. However, validated target mRNAs are sparse in number, and how their binding to Bicc1 is regulated remains poorly understood. Bicc1 recruitment to Dand5 transcripts requires a conserved AGACGUGAC motif in the 3′UTR. Here, we report an N6-methyladenosine (m6A) in this sequence that disrupts binding to Bicc1 K homology (KH) domains in vitro, in stark contrast to IGF2BPs and FMR1, where m6A promotes RNA recognition by KH domains. We discuss the possible implications of this finding for LR axis formation and for a related role of Bicc1 in regulating specific target mRNAs in the kidney.
Keywords
- Received April 15, 2025.
- Accepted June 21, 2025.
- Published by Cold Spring Harbor Laboratory Press for the RNA Society
This article, published in RNA, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
