Deciphering Disordered Regions Controlling Mrna Decay In Highthroughput Joseph H Lobel Nicholas T Ingolia by Joseph H. Lobel & Nicholas T. Ingolia 101038/S4158602508919X instant download after payment.

Intrinsically disordered regions within proteins drive specifc molecular functions Published online: xx xx xxxxdespite lacking a defned structure1,2. Although disordered regions are integral Check for updatesto controlling mRNA stability and translation, the mechanisms underlying these regulatory efects remain unclear3. Here we reveal the molecular determinants of this activity using high-throughput functional profling. Systematic mutagenesis across hundreds of regulatory disordered elements, combined with machine learning, reveals a complex pattern of molecular features important for their activity. The presence and arrangement of aromatic residues strongly predicts the ability of seemingly diverse protein sequences to infuence mRNA stability and translation. We further show how many of these regulatory elements exert their efects by engaging core mRNA decay machinery. Our results defne molecular features and biochemical pathways that explain how disordered regions control mRNA expression and shed light on broader principles within functional, unstructured proteins.