Poly(A)-specific ribonuclease (PARN): An allosterically regulated, processive and mRNA cap-interacting deadenylase

Virtanen, Anders; Henriksson, Niklas; Nilsson, Per; Nissbeck, Mikael

doi:10.3109/10409238.2013.771132

Cited by 62 publications

(94 citation statements)

References 152 publications

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“…PARN is highly conserved in higher eukaryotes, but is not identified in yeast and fly [2,4,5]. Previous functional studies have shown that PARN is involved in several crucial physiological processes such as the meiotic maturation of frog oocytes [49], embryogenesis and stress response in plants [50,51] and stage-specific protein production in Trypanosoma brucei [52].…”

Section: Discussionmentioning

confidence: 97%

“…Meanwhile, the depletion of Ccr4b/CNOT6L in NIH 3T3 cells increases the mRNA stability of p27 but not p21 [26]. Among the various deadenylases, PARN is unique due to its highly processive deadenylation activity in a cap-dependent manner (reviewed in [5]). PARN has been shown to participate in rapid deadenylation mediated by ARE [27], which has been shown to be a stabilizing element in the p21 mRNA.…”

Section: Introductionmentioning

confidence: 98%

“…By modulating the poly(A) tail length of mRNAs and mRNA fates thereby, deadenylases have been found to participate in many vital cellular processes such as mitotic division, oocyte maturation, differentiation and responses to various stresses [2,[4][5][6][7][8]. Whenever there is a need of metabolic changes, the fates of a certain subset of mRNAs will be regulated by either enhancing or decreasing mRNA stability.…”

Section: Introductionmentioning

confidence: 99%

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Depletion of poly(A)-specific ribonuclease (PARN) inhibits proliferation of human gastric cancer cells by blocking cell cycle progression

Zhang

Yan

2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Regulation of mRNA decay plays a crucial role in the post-transcriptional control of cell growth, survival, differentiation, death and senescence. Deadenylation is a rate-limiting step in the silence and degradation of the bulk of highly regulated mRNAs. However, the physiological functions of various deadenylases have not been fully deciphered. In this research, we found that poly(A)-specific ribonuclease (PARN) was upregulated in gastric tumor tissues and gastric cancer cell lines MKN28 and AGS. The cellular function of PARN was investigated by stably knocking down the endogenous PARN in the MKN28 and AGS cells. Our results showed that PARN-depletion significantly inhibited the proliferation of the two types of gastric cancer cells and promoted cell death, but did not significantly affect cell motility and invasion. The depletion of PARN arrested the gastric cancer cells at the G0/G1 phase by upregulating the expression levels of p53 and p21 but not p27. The mRNA stability of p53 was unaffected by PARN-knockdown in both types of cells. A significant stabilizing effect of PARN-depletion on p21 mRNA was observed in the AGS cells but not in the MKN28 cells. We further showed that the p21 3'-UTR triggered the action of PARN in the AGS cells. The dissimilar observations between the MKN28 and AGS cells as well as various stress conditions suggested that the action of PARN strongly relied on protein expression profiles of the cells, which led to heterogeneity in the stability of PARN-targeted mRNAs.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Depletion of poly(A)-specific ribonuclease (PARN) inhibits proliferation of human gastric cancer cells by blocking cell cycle progression

Zhang

Yan

2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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“…In human and murine liver cells, 3′ adenylation mediated by the nucleotidyl transferase PAPD4 has been shown to stabilize miR-122 (19). In contrast, PAPD5 was recently found to aid in the maturation of SNORA63 and other small nucleolar RNAs in a pathway where oligoadenylation by PAPD5 is followed by 3′-to-5′ trimming by the exonuclease PARN (38,39) (Fig. S6).…”

Section: Significancementioning

confidence: 99%

PAPD5-mediated 3′ adenylation and subsequent degradation of miR-21 is disrupted in proliferative disease

Boele

Persson

Shin

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

136

143

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Next-generation sequencing experiments have shown that microRNAs (miRNAs) are expressed in many different isoforms (isomiRs), whose biological relevance is often unclear. We found that mature miR-21, the most widely researched miRNA because of its importance in human disease, is produced in two prevalent isomiR forms that differ by 1 nt at their 3′ end, and moreover that the 3′ end of miR-21 is posttranscriptionally adenylated by the noncanonical poly(A) polymerase PAPD5. PAPD5 knockdown caused an increase in the miR-21 expression level, suggesting that PAPD5-mediated adenylation of miR-21 leads to its degradation. Exoribonuclease knockdown experiments followed by small-RNA sequencing suggested that PARN degrades miR-21 in the 3′-to-5′ direction. In accordance with this model, microarray expression profiling demonstrated that PAPD5 knockdown results in a down-regulation of miR-21 target mRNAs. We found that disruption of the miR-21 adenylation and degradation pathway is a general feature in tumors across a wide range of tissues, as evidenced by data from The Cancer Genome Atlas, as well as in the noncancerous proliferative disease psoriasis. We conclude that PAPD5 and PARN mediate degradation of oncogenic miRNA miR-21 through a tailing and trimming process, and that this pathway is disrupted in cancer and other proliferative diseases.nucleotidyl transferase | microRNA processing

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“…65 This was attributed to the decreased phosphorylation of 4EBP, which allows dephosphorylated 4EBP to disrupt the eIF4E-eIF4G interaction that binds the cap much more strongly than eIF4E alone (nanomolar range compared with low micromolar range). 65,89,99 PARN interacts with FXR1a-microRNP in G0 and in immature oocytes, indicating a role in microRNA-mediated translation activation (Fig. 1).…”

Section: Parn Is Essential For Fxr1a-micrornp Mediated Translation Asmentioning

confidence: 99%

FXR1a-associated microRNP: A driver of specialized non-canonical translation in quiescent conditions

Bukhari

Vasudevan

2017

RNA Biology

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Eukaryotic protein synthesis is a multifaceted process that requires coordination of a set of translation factors in a particular cellular state. During normal growth and proliferation, cells generally make their proteome via conventional translation that utilizes canonical translation factors. When faced with environmental stress such as growth factor deprivation, or in response to biological cues such as developmental signals, cells can reduce canonical translation. In this situation, cells adapt alternative modes of translation to make specific proteins necessary for required biological functions under these distinct conditions. To date, a number of alternative translation mechanisms have been reported, which include non-canonical, cap dependent translation and cap independent translation such as IRES mediated translation. Here, we discuss one of the alternative modes of translation mediated by a specialized microRNA complex, FXR1a-microRNP that promotes non-canonical, cap dependent translation in quiescent conditions, where canonical translation is reduced due to low mTOR activity.

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Poly(A)-specific ribonuclease (PARN): An allosterically regulated, processive and mRNA cap-interacting deadenylase

Cited by 62 publications

References 152 publications

Depletion of poly(A)-specific ribonuclease (PARN) inhibits proliferation of human gastric cancer cells by blocking cell cycle progression

Depletion of poly(A)-specific ribonuclease (PARN) inhibits proliferation of human gastric cancer cells by blocking cell cycle progression

PAPD5-mediated 3′ adenylation and subsequent degradation of miR-21 is disrupted in proliferative disease

FXR1a-associated microRNP: A driver of specialized non-canonical translation in quiescent conditions

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