TY - JOUR

T1 - PARP1 Regulates the Biogenesis and Activity of Telomerase Complex Through Modification of H/ACA-Proteins

AU - Savelyev, Nikita V.

AU - Shepelev, Nikita M.

AU - Lavrik, Olga I.

AU - Rubtsova, Maria P.

AU - Dontsova, Olga A.

N1 - Funding Information: This work was supported by Russian Foundation for Basic Research [18-29-07031 mk], Russian Science Foundation [19-14-00065], and Lomonosov Moscow State University Development Program. Publisher Copyright: © Copyright © 2021 Savelyev, Shepelev, Lavrik, Rubtsova and Dontsova. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/5/19

Y1 - 2021/5/19

N2 - Poly(ADP-ribose) polymerase 1 (PARP1) is established as a key regulator of the cellular DNA damage response and apoptosis. In addition, PARP1 participates in the global regulation of DNA repair, transcription, telomere maintenance, and inflammation response by modulating various DNA-protein and protein-protein interactions. Recently, it was reported that PARP1 also influences splicing and ribosomal RNA biogenesis. The H/ACA ribonucleoprotein complex is involved in a variety of cellular processes such as RNA maturation. It contains non-coding RNAs with specific H/ACA domains and four proteins: dyskerin (DKC1), GAR1, NHP2, and NOP10. Two of these proteins, DKC1 and GAR1, are targets of poly(ADP-ribosyl)ation catalyzed by PARP1. The H/ACA RNA-binding proteins are involved in the regulation of maturation and activity of the telomerase complex, which maintains telomere length. In this study, we demonstrated that of poly(ADP-ribosyl)ation influences on RNA-binding properties of DKC1 and GAR1 and telomerase assembly and activity. Our data provide the evidence that poly(ADP-ribosyl)ation regulates telomerase complex assembly and activity, in turn regulating telomere length that may be useful for design and development of anticancer therapeutic approaches that are based on the inhibition of PARP1 and telomerase activities.

AB - Poly(ADP-ribose) polymerase 1 (PARP1) is established as a key regulator of the cellular DNA damage response and apoptosis. In addition, PARP1 participates in the global regulation of DNA repair, transcription, telomere maintenance, and inflammation response by modulating various DNA-protein and protein-protein interactions. Recently, it was reported that PARP1 also influences splicing and ribosomal RNA biogenesis. The H/ACA ribonucleoprotein complex is involved in a variety of cellular processes such as RNA maturation. It contains non-coding RNAs with specific H/ACA domains and four proteins: dyskerin (DKC1), GAR1, NHP2, and NOP10. Two of these proteins, DKC1 and GAR1, are targets of poly(ADP-ribosyl)ation catalyzed by PARP1. The H/ACA RNA-binding proteins are involved in the regulation of maturation and activity of the telomerase complex, which maintains telomere length. In this study, we demonstrated that of poly(ADP-ribosyl)ation influences on RNA-binding properties of DKC1 and GAR1 and telomerase assembly and activity. Our data provide the evidence that poly(ADP-ribosyl)ation regulates telomerase complex assembly and activity, in turn regulating telomere length that may be useful for design and development of anticancer therapeutic approaches that are based on the inhibition of PARP1 and telomerase activities.

KW - biogenesis

KW - H/ACA-proteins

KW - poly(ADP-Ribose) polymerase 1

KW - ribonucleorprotein complex

KW - telomerase

KW - telomere

UR - http://www.scopus.com/inward/record.url?scp=85107214099&partnerID=8YFLogxK

U2 - 10.3389/fcell.2021.621134

DO - 10.3389/fcell.2021.621134

M3 - Article

C2 - 34095104

AN - SCOPUS:85107214099

VL - 9

JO - Frontiers in Cell and Developmental Biology

JF - Frontiers in Cell and Developmental Biology

SN - 2296-634X

M1 - 621134

ER -