التفاصيل البيبلوغرافية
| العنوان: |
Defining the mechanisms and properties of post-transcriptional regulatory disordered regions by high-throughput functional profiling. |
| المؤلفون: |
Lobel JH; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA., Ingolia NT; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.; Lead contact. |
| المصدر: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Feb 05. Date of Electronic Publication: 2024 Feb 05. |
| نوع المنشور: |
Preprint |
| اللغة: |
English |
| بيانات الدورية: |
Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: |
Disordered regions within RNA binding proteins are required to control mRNA decay and protein synthesis. To understand how these disordered regions modulate gene expression, we surveyed regulatory activity across the entire disordered proteome using a high-throughput functional assay. We identified hundreds of regulatory sequences within intrinsically disordered regions and demonstrate how these elements cooperate with core mRNA decay machinery to promote transcript turnover. Coupling high-throughput functional profiling with mutational scanning revealed diverse molecular features, ranging from defined motifs to overall sequence composition, underlying the regulatory effects of disordered peptides. Machine learning analysis implicated aromatic residues in particular contexts as critical determinants of repressor activity, consistent with their roles in forming protein-protein interactions with downstream effectors. Our results define the molecular principles and biochemical mechanisms that govern post-transcriptional gene regulation by disordered regions and exemplify the encoding of diverse yet specific functions in the absence of well-defined structure.
Competing Interests: Declaration of interests: N.T.I holds equity and serves as a scientific advisor to Tevard Biosciences, and holds equity in Velia Therapeutics. |
| معلومات مُعتمدة: |
F32 GM148044 United States GM NIGMS NIH HHS; R01 GM130996 United States GM NIGMS NIH HHS; S10 OD018174 United States OD NIH HHS |
| تواريخ الأحداث: |
Date Created: 20240219 Latest Revision: 20240226 |
| رمز التحديث: |
20240226 |
| مُعرف محوري في PubMed: |
PMC10871298 |
| DOI: |
10.1101/2024.02.01.578453 |
| PMID: |
38370681 |
| قاعدة البيانات: |
MEDLINE |
