ELOA3 : A primate-specific RNA polymerase II elongation factor encoded by a tandem repeat gene cluster

The biological role of the repetitive DNA sequences in the human genome remains an outstanding question. Recent long-read human genome assemblies have allowed us to identify a function for one of these repetitive regions. We have uncovered a tandem array of conserved primate-specific retrogenes enco...

Full description

Saved in:
Bibliographic Details
Published in:Science advances 2023-11, Vol.9 (47), p.eadj1261
Main Authors: Morgan, Marc A J, Mohammad Parast, Saeid, Iwanaszko, Marta, Aoi, Yuki, Yoo, DongAhn, Dumar, Zachary J, Howard, Benjamin C, Helmin, Kathryn A, Liu, Qianli, Thakur, William R, Zeidner, Jacob M, Singer, Benjamin D, Eichler, Evan E, Shilatifard, Ali
Format: Article
Language:English
Subjects:
Animals
Elongin - genetics
Humans
Multigene Family
Peptide Elongation Factors - genetics
Primates - genetics
RNA Polymerase II - genetics
RNA Polymerase II - metabolism
Tandem Repeat Sequences - genetics
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The biological role of the repetitive DNA sequences in the human genome remains an outstanding question. Recent long-read human genome assemblies have allowed us to identify a function for one of these repetitive regions. We have uncovered a tandem array of conserved primate-specific retrogenes encoding the protein Elongin A3 (ELOA3), a homolog of the RNA polymerase II (RNAPII) elongation factor Elongin A (ELOA). Our genomic analysis shows that the gene cluster is conserved among primates and the number of gene repeats is variable in the human population and across primate species. Moreover, the gene cluster has undergone concerted evolution and homogenization within primates. Our biochemical studies show that ELOA3 functions as a promoter-associated RNAPII pause-release elongation factor with distinct biochemical and functional features from its ancestral homolog, ELOA. We propose that the gene cluster has evolved to fulfil a transcriptional regulatory function unique to the primate lineage that can be targeted to regulate cellular hyperproliferation.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.adj1261