Vault RNA1–1 riboregulates the autophagic function of p62 by binding to lysine 7 and arginine 21, both of which are critical for p62 oligomerization

Title data

Büscher, Magdalena ; Horos, Rastislav ; Huppertz, Ina ; Haubrich, Kevin ; Dobrev, Nikolay ; Baudin, Florence ; Hennig, Janosch ; Hentze, Matthias W.:
Vault RNA1–1 riboregulates the autophagic function of p62 by binding to lysine 7 and arginine 21, both of which are critical for p62 oligomerization.
In: RNA : a Publication of the RNA Society. Vol. 28 (2022) Issue 5 . - pp. 742-755.
ISSN 1469-9001
DOI: https://doi.org/10.1261/rna.079129.122

Official URL:

Abstract in another language

Cellular processes can be regulated at multiple levels, including transcriptional, post-transcriptional, and post-translational mechanisms. We have recently shown that the small, noncoding vault RNA1-1 negatively riboregulates p62 oligomerization in selective autophagy through direct interaction with the autophagic receptor. This function is highly specific for this Pol III transcript, but the determinants of this specificity and a mechanistic explanation of how vault RNA1-1 inhibits p62 oligomerization are lacking. Here, we combine biochemical and functional experiments to answer these questions. We show that the PB1 domain and adjacent linker region of p62 (aa 1-122) are necessary and sufficient for specific vault RNA1-1 binding, and we identify lysine 7 and arginine 21 as key hinges for p62 riboregulation. Chemical structure probing of vault RNA1-1 further reveals a central flexible loop within vault RNA1-1 that is required for the specific interaction with p62. Overall, our data provide molecular insight into how a small RNA riboregulates protein-protein interactions critical to the activation of specific autophagy.

Further data

Item Type:	Article in a journal
Refereed:	Yes
Institutions of the University:	Faculties Faculties > Faculty of Biology, Chemistry and Earth Sciences Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry with an Emphasis on Biophysical Chemistry Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry with an Emphasis on Biophysical Chemistry > Chair Biochemistry with an Emphasis on Biophysical Chemistry - Univ.-Prof. Dr. Janosch Hennig
Result of work at the UBT:	No
DDC Subjects:	500 Science > 500 Natural sciences 500 Science > 540 Chemistry 500 Science > 570 Life sciences, biology
Date Deposited:	27 May 2022 07:30
Last Modified:	19 Oct 2022 13:27
URI:	https://eref.uni-bayreuth.de/id/eprint/69769