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A low-complexity region in the YTH domain protein Mmi1 enhances RNA binding

DOI: 10.1074/jbc.RA118.002291 DOI Help

Authors: James A. W. Stowell (MRC Laboratory of Molecular Biology) , Jane L. Wagstaff (MRC Laboratory of Molecular Biology) , Chris H. Hill (MRC Laboratory of Molecular Biology) , Minmin Yu (MRC Laboratory of Molecular Biology) , Stephen H. Mclaughlin (MRC Laboratory of Molecular Biology) , Stefan M. V. Freund (MRC Laboratory of Molecular Biology) , Lori A. Passmore (MRC Laboratory of Molecular Biology)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Biological Chemistry

State: Published (Approved)
Published: April 2018
Diamond Proposal Number(s): 8547 , 11235

Open Access Open Access

Abstract: Mmi1 is an essential RNA-binding protein in the fission yeast Schizosaccharomyces pombe that eliminates meiotic transcripts during normal vegetative growth. Mmi1 contains a YTH domain that binds specific RNA sequences, targeting mRNAs for degradation. The YTH domain of Mmi1 uses a noncanonical RNA-binding surface that includes contacts outside the conserved fold. Here, we report that an N-terminal extension that is proximal to the YTH domain enhances RNA binding. Using X-ray crystallography, NMR and biophysical methods, we show that this low-complexity region becomes more ordered upon RNA binding. This enhances the affinity of the interaction of the Mmi1 YTH domain with specific RNAs by reducing the dissociation rate of the Mmi1–RNA complex. We propose that the low-complexity region influences RNA binding indirectly by reducing dynamic motions of the RNA binding groove and stabilizing a conformation of the YTH domain that binds to RNA with high affinity. Taken together, our work reveals how a low-complexity region proximal to a conserved folded domain can adopt an ordered structure to aid nucleic acid binding.

Journal Keywords: YTH domain; exosome specificity factor; YT521-B homology; deadenylation; protein-nucleic acid interaction; RNA binding protein; mRNA decay; meiosis; nuclear magnetic resonance (NMR); intrinsically disordered protein

Subject Areas: Biology and Bio-materials

Instruments: I02-Macromolecular Crystallography , I03-Macromolecular Crystallography

Added On: 09/05/2018 09:50


Discipline Tags:

Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)