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

Published on May 19, 2021in Frontiers in Cell and Developmental Biology5.201
· DOI :10.3389/FCELL.2021.621134
Nikita Savelyev1
Estimated H-index: 1
Nikita M. Shepelev + 2 AuthorsOlga A. Dontsova34
Estimated H-index: 34
#1Rebekah Eleazer (UK: University of Kentucky)H-Index: 4
#2Yvonne N. Fondufe-Mittendorf (UK: University of Kentucky)H-Index: 19
Poly(ADP-ribose) polymerases (PARPs) are abundant nuclear proteins that synthesize ADP ribose polymers (pADPr) and catalyze the addition of (p)ADPr to target biomolecules. PARP1, the most abundant and well-studied PARP, is a multifunctional enzyme that participates in numerous critical cellular processes. A considerable amount of PARP research has focused on PARP1's role in DNA damage. However, an increasing body of evidence outlines more routine roles for PARP and PARylation in nearly every ste...
3 CitationsSource
#1Song My Hoang (University of Pittsburgh)H-Index: 2
#2Nicole Kaminski (University of Pittsburgh)H-Index: 1
Last. Roderick J. O’Sullivan (University of Pittsburgh)H-Index: 11
view all 22 authors...
The synthesis of poly(ADP-ribose) (PAR) reconfigures the local chromatin environment and recruits DNA-repair complexes to damaged chromatin. PAR degradation by poly(ADP-ribose) glycohydrolase (PARG) is essential for progression and completion of DNA repair. Here, we show that inhibition of PARG disrupts homology-directed repair (HDR) mechanisms that underpin alternative lengthening of telomeres (ALT). Proteomic analyses uncover a new role for poly(ADP-ribosyl)ation (PARylation) in regulating the...
#1Elena A. Matveeva (UK: University of Kentucky)H-Index: 15
#2Lein F. Mathbout (Alfaisal University)H-Index: 1
Last. Yvonne N. Fondufe-Mittendorf (UK: University of Kentucky)H-Index: 19
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PARP1 is an abundant nuclear protein with many pleiotropic functions involved in epigenetic and transcriptional controls. Abundance of mRNA depends on the balance between synthesis and decay of a particular transcript. PARP1 binds RNA and its depletion results in increased expression of genes involved in nonsense-mediated decay, suggesting that PARP1 might be involved in mRNA stability. This is of interest considering RNA binding proteins play key roles in post-transcriptional processes in all e...
6 CitationsSource
#1Elena A. Matveeva (UK: University of Kentucky)H-Index: 15
#2Qamar M. H. Al-Tinawi (Alfaisal University)H-Index: 1
Last. Yvonne N. Fondufe-Mittendorf (UK: University of Kentucky)H-Index: 19
view all 4 authors...
Background Recently, we showed that PARP1 is involved in cotranscriptional splicing, possibly by bridging chromatin to RNA and recruiting splicing factors. It also can influence alternative splicing decisions through the regulation of RNAPII elongation. In this study, we investigated the effect of PARP1-mediated chromatin changes on RNAPII movement, during transcription and alternative splicing.
17 CitationsSource
For more than a decade, it has been known that mammalian cells use shelterin to protect chromosome ends. Much progress has been made on the mechanism by which shelterin prevents telomeres from inad...
204 CitationsSource
#1Marie-France Langelier (UdeM: Université de Montréal)H-Index: 23
#2Travis J Eisemann (UdeM: Université de Montréal)H-Index: 3
Last. John M. Pascal (UdeM: Université de Montréal)H-Index: 36
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Poly(ADP-ribose) is a posttranslational modification and signaling molecule that regulates many aspects of human cell biology, and it is synthesized by enzymes known as poly(ADP-ribose) polymerases, or PARPs. A diverse collection of domain structures dictates the different cellular roles of PARP enzymes and regulates the production of poly(ADP-ribose). Here we primarily review recent structural insights into the regulation and catalysis of two family members: PARP-1 and Tankyrase. PARP-1 has mul...
54 CitationsSource
#1Manana Melikishvili (UK: University of Kentucky)H-Index: 9
#2Julia H. Chariker (University of Louisville)H-Index: 11
Last. Yvonne N. Fondufe-Mittendorf (UK: University of Kentucky)H-Index: 19
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Recent studies implicate Poly (ADP-ribose) polymerase 1 (PARP1) in alternative splicing regulation, and PARP1 may be an RNA-binding protein. However, detailed knowledge of RNA targets and the RNA-binding region for PARP1 are unknown. Here we report the first global study of PARP1–RNA interactions using PAR–CLIP in HeLa cells. We identified a largely overlapping set of 22 142 PARP1–RNA-binding peaks mapping to mRNAs, with 20 484 sites located in intronic regions. PARP1 preferentially bound RNA co...
27 CitationsSource
#1Meng Hsun Hsieh (NTU: National Taiwan University)H-Index: 1
#2Yi Ting Chen (NTU: National Taiwan University)H-Index: 1
Last. Shu-Chun Teng (NTU: National Taiwan University)H-Index: 28
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Abstract Telomerase is highly expressed in cancer and embryonic stem cells (ESCs) and implicated in controlling genome integrity, cancer formation and stemness. Previous studies identified that Kruppel-like transcription factor 4 (KLF4) activates telomerase reverse transcriptase (TERT) expression and contributes to the maintenance of self-renewal in ESCs. However, little is known about how KLF4 regulates TERT expression. Here, we discover poly(ADP-ribose) polymerase 1 (PARP1) as a novel KLF4-int...
20 CitationsSource
#1Isabelle Schmutz (Rockefeller University)H-Index: 16
#2Leonid A. Timashev (Rockefeller University)H-Index: 3
Last. Titia de Lange (Rockefeller University)H-Index: 92
view all 5 authors...
Functional analysis of TRF2-RuvC chimeras establishes that binding of the TRF2 basic domain to branched-DNA structures of the t-loop is responsible for telomere protection in mouse and human cells.
31 CitationsSource
#1Séverine Massenet (University of Lorraine)H-Index: 17
#2Edouard Bertrand (University of Montpellier)H-Index: 66
Last. Céline Verheggen (University of Montpellier)H-Index: 26
view all 3 authors...
ABSTRACTBox C/D and box H/ACA snoRNAs are abundant non-coding RNAs that localize in the nucleolus and mostly function as guides for nucleotide modifications. While a large pool of snoRNAs modifies rRNAs, an increasing number of snoRNAs could also potentially target mRNAs. ScaRNAs belong to a family of specific RNAs that localize in Cajal bodies and that are structurally similar to snoRNAs. Most scaRNAs are involved in snRNA modification, while telomerase RNA, which contains H/ACA motifs, functio...
70 CitationsSource
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