Biology subjects

Albihlal, W. S.

Publications and source records attributed to Albihlal, W. S..

2 recordsLinked to original sources

bioRxiv2026

Cellular context restricts a promiscuous m6A reader IDR to a single functional effector interface for mRNA decay

N6-methyladenosine (m6A) is a conserved mRNA modification that regulates transcript stability, yet how m6A readers engage effectors remains unknown. We show that during yeast meiosis, the YTH-domain protein Pho92 promotes the decay of m6A-modified transcripts through an uncharacterised, promiscuous intrinsically disordered region (IDR). In vitro, the Pho92 IDR makes multiple contacts with the Ccr4-NOT deadenylase complex and drives tethered reporter decay in the absence of any single subunit. Yet in meiosis, turnover of endogenous m6A-modified transcripts strictly depends on a single interface: direct binding of the Pho92 IDR to Caf40. A single hydrophobic residue substitution is sufficient to abolish Caf40 binding and halt transcript decay. Human YTHDF proteins can functionally substitute for Pho92, but require multiple hydrophobic patches within the IDR for decay activity. Thus, on endogenous m6A-modified transcripts during meiosis, the promiscuous Pho92 IDR is restricted to a single functional interface, revealing unappreciated specificity in m6A-directed mRNA decay.

molecular biology↗

bioRxiv2021

The mechanical regulation of RNA binding protein hnRNPC in the failing heart

Cardiac pathologies are characterized by intense remodeling of the extracellular matrix (ECM) that eventually leads to heart failure. Cardiomyocytes respond to the ensuing biomechanical stress by re-expressing fetal contractile proteins via transcriptional and post-transcriptional processes, like alternative splicing (AS). Here, we demonstrate that the heterogeneous nuclear ribonucleoprotein C (hnRNPC) is upregulated and relocates to the sarcomeric Z-disk upon ECM pathological remodeling. We show that this is an active site of localized translation, where the ribonucleoprotein associates to the translation machinery. Alterations in hnRNPC expression and localization can be mechanically determined and affect the AS of numerous mRNAs involved in mechanotransduction and cardiovascular diseases, like Hippo pathway effector YAP1. We propose that cardiac ECM remodeling serves as a switch in RNA metabolism by impacting an associated regulatory protein of the spliceosome apparatus. These findings offer new insights on the mechanism of mRNAs homeostasis mechanoregulation in pathological conditions.

pathology↗