RNA Control by Protein Complexes in Germline Stem Cells

Date

2020-05

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Abstract

RNA regulation is central to controlling gene expression. PUF proteins are posttranscriptional regulators that bind specific 3’ untranslated sequences of target mRNAs through their conserved RNA-binding domains (RBDs). In this work, we explore the specificity of these factors and their mechanisms of action in Caenorhabditis elegans germline stem cell (GSC) control. Caenorhabditis elegans PUF proteins FBF-2 (binds a 9-nt element) and PUF-8 (binds an 8-nt element) promote germline stem cell maintenance and differentiation respectively. A reprogrammed FBF-2 with mutations in a few base-interacting residues allowed a switch in binding specificity to a shorter 8- nucleotide element recognized by PUF8. Mutant FBF-2 successfully rescued a proliferative defect caused by the absence of PUF8 function. Binding of FBF-2 to LST-1, a GSC regulator and PUF protein partner, restricts FBF-2 specificity. We also observed dynamic structural changes in the FBF-2 RBD scaffold in a ternary complex with RNA and LST-1. These results present key insights into PUF proteins’ mechanism of action in stem cell regulation.

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X-ray crystallography, Developmental biology, Molecular biology, RNA-protein interactions, Caenorhabditis elegans

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©2020 Vandita Dattatraya Bhat. All rights reserved.

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