Deciphering disordered regions controlling mRNA decay in high-throughput

Joseph H. Lobel and Nicholas T. Ingolia ()
Additional contact information
Joseph H. Lobel: University of California, Berkeley
Nicholas T. Ingolia: University of California, Berkeley

Nature, 2025, vol. 642, issue 8068, 805-813

Abstract: Abstract Intrinsically disordered regions within proteins drive specific molecular functions despite lacking a defined structure1,2. Although disordered regions are integral to controlling mRNA stability and translation, the mechanisms underlying these regulatory effects remain unclear3. Here we reveal the molecular determinants of this activity using high-throughput functional profiling. 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 influence mRNA stability and translation. 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 pathways that explain how disordered regions control mRNA expression and shed light on broader principles within functional, unstructured proteins.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-025-08919-x Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:642:y:2025:i:8068:d:10.1038_s41586-025-08919-x

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-025-08919-x

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().