Coordinated Action of Two Double-Stranded RNA Binding Motifs and an RGG Motif Enables Nuclear Factor 90 To Flexibly Target Different RNA Substrates

Biochemistry
Tobias SchmidtSven-Erik Behrens

Abstract

The mechanisms of how RNA binding proteins (RBP) bind to and distinguish different RNA molecules are yet uncertain. Here, we performed a comprehensive analysis of the RNA binding properties of multidomain RBP nuclear factor 90 (NF90) by investigating specifically the functional activities of two double-stranded RNA binding motifs (dsRBM) and an RGG motif in the protein's unstructured C-terminus. By comparison of the RNA binding affinities of several NF90 variants and their modes of binding to a set of defined RNA molecules, the activities of the motifs turned out to be very different. While dsRBM1 contributes little to RNA binding, dsRBM2 is essential for effective binding of double-stranded RNA. The protein's immediate C-terminus, including the RGG motif, is indispensable for interactions of the protein with single-stranded RNA, and the RGG motif decisively contributes to NF90's overall RNA binding properties. Conformational studies, which compared wild-type NF90 with a variant that contains a pseudophosphorylated residue in the RGG motif, suggest that the NF90 C-terminus is involved in conformational changes in the protein after RNA binding, with the RGG motif acting as a central regulatory element. In summary, our data propo...Continue Reading

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Citations

Aug 10, 2018·Wiley Interdisciplinary Reviews. RNA·Manuel Garcia-MorenoAlfredo Castello
Oct 2, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Francesca FasoloStefano Gustincich
Nov 9, 2019·Nucleic Acids Research·Samir F WatsonSara Macias
Mar 4, 2020·Cell Death Discovery·Donglin DingWei Jiang
Feb 7, 2020·Nucleic Acids Research·Volker NitschkoKlaus Förstemann
Jan 22, 2021·Cell Death Discovery·Donglin DingWei Jiang

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