“Global Analysis of the Networks Controlling mRNA Translation and Decay”
Nicholas Ingolia | Berkeley
Intrinsically disordered regions within proteins drive specific molecular functions despite lacking a defined structure. While disordered regions are integral to controlling mRNA stability and translation, the mechanisms underlying these regulatory effects remain unclear. We reveal the molecular determinants of this activity using high-throughput functional profiling. Systematic mutagenesis across hundreds of functional elements, combined with machine learning, reveals a complex molecular grammar for regulatory disordered regions. The presence and arrangement of aromatic residues strongly predicts regulatory activity of seemingly diverse protein sequences. We further show how many of these regulatory elements exert their effects by engaging core mRNA decay machinery. Our results define molecular features and biochemical mechanisms explaining how disordered regions control mRNA expression and shed light on broader principles within functional, unstructured proteins.protocols.
