Talk abstracts
Talk on Friday 03:15-03:30pm submitted by Gabrielle Schuh
Repression of Ago1 by Ago2 via let-7 microRNAs facilitates embryonic stem cell differentiation
Gabrielle M. Schuh (Biochemistry and molecular biology, Mayo Clinic), Katharine R. Maschhoff (Biochemistry and molecular biology, Mayo Clinic), Annastasia Minor (Biochemistry and molecular biology, Mayo Clinic), Wenqian Hu (Biochemistry and molecular biology, Mayo Clinic)
Abstract:
Argonaute (AGO) proteins are critical regulators of gene expression. Of the four AGOs in mammals, AGO1 and AGO2 are expressed in mouse embryonic stem cells (mESCs). These two proteins have opposing functions in controlling the fate decisions between pluripotency and differentiation in mESCs. AGO2 promotes differentiation predominantly via the let-7 microRNAs, whereas AGO1 maintains pluripotency via modulating protein folding independent of small RNAs. These recent findings raise the question of whether and how these two AGOs are mutually regulated in mESCs. Here, using loss-of-function and gain-of-function approaches, we show that AGO2 represses the expression of Ago1 mRNA via a conserved let-7-microRNA-binding site in its 3’UTR. Mutating this binding site at the endogenous locus abolishes the AGO2-mediated repression of Ago1 mRNA and compromises the exit pluripotency of mESCs. These results reveal that the post-transcriptional regulation of Ago1 by Ago2 and let-7 microRNAs is important for proper stem cell fate decisions.
References:
Qiuying Liu, Xiaoli Chen, Mariah K Novak, Shaojie Zhang, Wenqian Hu (2021) Repressing Ago2 mRNA translation by Trim71 maintains pluripotency through inhibiting let-7 microRNAs. eLife 10:e66288.
Qiuying Liu, Rachel M Pepin, Mariah K Novak, Katharine R Maschhoff, Kailey Worner, Wenqian Hu (2024) AGO1 controls protein folding in mouse embryonic stem cell fate decisions. Developmental Cell 10.1016
Keywords: let-7 microRNA, Argonaute proteins, embryonic stem cell differentiation