Year: 2023
Type: article
Abstract: Over the past decade, advances in genomics have identified thousands of additional protein-coding small open reading frames (smORFs) missed by traditional gene finding approaches. These smORFs encode peptides and small proteins, commonly termed micropeptides or microproteins. Several of these newly discovered microproteins have biological functions and operate through interactions with proteins and protein complexes within the cell. CYREN1 is a characterized microprotein that regulates double-strand break repair in mammalian cells through interaction with Ku70/80 heterodimer. Ku70/80 binds to and stabilizes double-strand breaks and recruits the machinery needed for nonhomologous end join repair. In this study, we examined the biochemical properties of CYREN1 to better understand and explain its cellular protein interactions. Our findings support that CYREN1 is an intrinsically disordered microprotein and this disordered structure allows it to enriches several proteins, including a newly discovered interaction with SF3B1 via a distinct short linear motif (SLiMs) on CYREN1. Since many microproteins are predicted to be disordered, CYREN1 is an exemplar of how microproteins interact with other proteins and reveals an unknown scaffolding function of this microprotein that may link NHEJ and splicing.
Source: Biochemistry
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Pharmacological targeting of circadian clock components to treat glioblastoma, Mechanisms for regulation of a novel class of anti-diabetic lipids, Probing the biochemical mechanism of amyloid disease, Protein-protein interactions in natural product biosynthesis, Cancer Center Support Grant (CCSG), The Discovery of Human Peptide Encoding Genes, An Encyclopedia of the Adipose Tissue Secretome to Identify Mediators of Health and Disease
OpenAlex ID: W4387472839