The HAPSTR2 retrogene buffers stress signaling and resilience in mammals

David R. Amici, Harun Cingoz, Milad J. Alasady, Sammy Alhayek, Claire M. Phoumyvong, Nidhi Sahni, S. Stephen Yi and Marc L. Mendillo ()
Additional contact information
David R. Amici: Northwestern University Feinberg School of Medicine
Harun Cingoz: Northwestern University Feinberg School of Medicine
Milad J. Alasady: Northwestern University Feinberg School of Medicine
Sammy Alhayek: Northwestern University Feinberg School of Medicine
Claire M. Phoumyvong: Northwestern University Feinberg School of Medicine
Nidhi Sahni: The University of Texas MD Anderson Cancer Center
S. Stephen Yi: The University of Texas at Austin
Marc L. Mendillo: Northwestern University Feinberg School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: Abstract We recently identified HAPSTR1 (C16orf72) as a key component in a novel pathway which regulates the cellular response to molecular stressors, such as DNA damage, nutrient scarcity, and protein misfolding. Here, we identify a functional paralog to HAPSTR1: HAPSTR2. HAPSTR2 formed early in mammalian evolution, via genomic integration of a reverse transcribed HAPSTR1 transcript, and has since been preserved under purifying selection. HAPSTR2, expressed primarily in neural and germline tissues and a subset of cancers, retains established biochemical features of HAPSTR1 to achieve two functions. In normal physiology, HAPSTR2 directly interacts with HAPSTR1, markedly augmenting HAPSTR1 protein stability in a manner independent from HAPSTR1’s canonical E3 ligase, HUWE1. Alternatively, in the context of HAPSTR1 loss, HAPSTR2 expression is sufficient to buffer stress signaling and resilience. Thus, we discover a mammalian retrogene which safeguards fitness.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-35697-1 Abstract (text/html)

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:natcom:v:14:y:2023:i:1:d:10.1038_s41467-022-35697-1

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

DOI: 10.1038/s41467-022-35697-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

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