From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens
"PARN" redirects here. For the surname, see
Pärn .
Poly(A)-specific ribonuclease (PARN) , also known as polyadenylate-specific ribonuclease or deadenylating nuclease (DAN) , is an
enzyme that in humans is encoded by the PARN
gene .
[5]
[6]
Function
Exonucleolytic degradation of the
poly(A) tail is often the first step in the decay of eukaryotic
mRNAs . The amino acid sequence of poly(A)-specific ribonuclease shows homology to the
RNase D family of 3'-
exonucleases . The protein appears to be localized in both the nucleus and the cytoplasm. It is not stably associated with polysomes or ribosomal subunits.
[6] Hereditary mutations in PARN lead to the bone marrow failure disease
dyskeratosis congenita which is caused by defective telomerase RNA processing and degradation in patients.
[7]
[8]
[9]
[10]
[11]
[12]
[13]
References
^
a
b
c
ENSG00000274829 GRCh38: Ensembl release 89: ENSG00000140694, ENSG00000274829 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000022685 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ Buiting K, Körner C, Ulrich B, Wahle E, Horsthemke B (May 2000). "The human gene for the poly(A)-specific ribonuclease (PARN) maps to 16p13 and has a truncated copy in the Prader-Willi/Angelman region on 15q11→q13". Cytogenetics and Cell Genetics . 87 (1–2): 125–31.
doi :
10.1159/000015378 .
PMID
10640832 .
S2CID
28498478 .
^
a
b
"Entrez Gene: PARN poly(A)-specific ribonuclease (deadenylation nuclease)" .
^ Tummala H, Walne A, Collopy L, Cardoso S, de la Fuente J, Lawson S, Powell J, Cooper N, Foster A, Mohammed S, Plagnol V, Vulliamy T, Dokal I (May 2015).
"Poly(A)-specific ribonuclease deficiency impacts telomere biology and causes dyskeratosis congenita" . The Journal of Clinical Investigation . 125 (5): 2151–60.
doi :
10.1172/JCI78963 .
PMC
4463202 .
PMID
25893599 .
^ Dhanraj S, Gunja SM, Deveau AP, Nissbeck M, Boonyawat B, Coombs AJ, Renieri A, Mucciolo M, Marozza A, Buoni S, Turner L, Li H, Jarrar A, Sabanayagam M, Kirby M, Shago M, Pinto D, Berman JN, Scherer SW, Virtanen A, Dror Y (November 2015). "Bone marrow failure and developmental delay caused by mutations in poly(A)-specific ribonuclease (PARN)". Journal of Medical Genetics . 52 (11): 738–48.
doi :
10.1136/jmedgenet-2015-103292 .
PMID
26342108 .
S2CID
19822046 .
^ Stuart BD, Choi J, Zaidi S, Xing C, Holohan B, Chen R, Choi M, Dharwadkar P, Torres F, Girod CE, Weissler J, Fitzgerald J, Kershaw C, Klesney-Tait J, Mageto Y, Shay JW, Ji W, Bilguvar K, Mane S, Lifton RP, Garcia CK (May 2015).
"Exome sequencing links mutations in PARN and RTEL1 with familial pulmonary fibrosis and telomere shortening" . Nature Genetics . 47 (5): 512–7.
doi :
10.1038/ng.3278 .
PMC
4414891 .
PMID
25848748 .
^ Shukla S, Schmidt JC, Goldfarb KC, Cech TR, Parker R (April 2016).
"Inhibition of telomerase RNA decay rescues telomerase deficiency caused by dyskerin or PARN defects" . Nature Structural & Molecular Biology . 23 (4): 286–92.
doi :
10.1038/nsmb.3184 .
PMC
4830462 .
PMID
26950371 .
^ Tseng CK, Wang HF, Burns AM, Schroeder MR, Gaspari M, Baumann P (December 2015).
"Human Telomerase RNA Processing and Quality Control" . Cell Reports . 13 (10): 2232–43.
doi :
10.1016/j.celrep.2015.10.075 .
PMID
26628367 .
^ Nguyen D, Grenier St-Sauveur V, Bergeron D, Dupuis-Sandoval F, Scott MS, Bachand F (December 2015).
"A Polyadenylation-Dependent 3' End Maturation Pathway Is Required for the Synthesis of the Human Telomerase RNA" . Cell Reports . 13 (10): 2244–57.
doi :
10.1016/j.celrep.2015.11.003 .
PMID
26628368 .
^ Moon DH, Segal M, Boyraz B, Guinan E, Hofmann I, Cahan P, Tai AK, Agarwal S (December 2015).
"Poly(A)-specific ribonuclease (PARN) mediates 3'-end maturation of the telomerase RNA component" . Nature Genetics . 47 (12): 1482–8.
doi :
10.1038/ng.3423 .
PMC
4791094 .
PMID
26482878 .
Further reading
Körner CG, Wahle E (April 1997).
"Poly(A) tail shortening by a mammalian poly(A)-specific 3'-exoribonuclease" . The Journal of Biological Chemistry . 272 (16): 10448–56.
doi :
10.1074/jbc.272.16.10448 .
PMID
9099687 .
Körner CG, Wormington M, Muckenthaler M, Schneider S, Dehlin E, Wahle E (September 1998).
"The deadenylating nuclease (DAN) is involved in poly(A) tail removal during the meiotic maturation of Xenopus oocytes" . The EMBO Journal . 17 (18): 5427–37.
doi :
10.1093/emboj/17.18.5427 .
PMC
1170868 .
PMID
9736620 .
Dehlin E, Wormington M, Körner CG, Wahle E (March 2000).
"Cap-dependent deadenylation of mRNA" . The EMBO Journal . 19 (5): 1079–86.
doi :
10.1093/emboj/19.5.1079 .
PMC
305646 .
PMID
10698948 .
Martinez J, Ren YG, Thuresson AC, Hellman U, Astrom J, Virtanen A (August 2000).
"A 54-kDa fragment of the Poly(A)-specific ribonuclease is an oligomeric, processive, and cap-interacting Poly(A)-specific 3' exonuclease" . The Journal of Biological Chemistry . 275 (31): 24222–30.
doi :
10.1074/jbc.M001705200 .
PMID
10801819 .
Gao M, Fritz DT, Ford LP, Wilusz J (March 2000).
"Interaction between a poly(A)-specific ribonuclease and the 5' cap influences mRNA deadenylation rates in vitro" . Molecular Cell . 5 (3): 479–88.
doi :
10.1016/S1097-2765(00)80442-6 .
PMC
2811581 .
PMID
10882133 .
Gao M, Wilusz CJ, Peltz SW, Wilusz J (March 2001).
"A novel mRNA-decapping activity in HeLa cytoplasmic extracts is regulated by AU-rich elements" . The EMBO Journal . 20 (5): 1134–43.
doi :
10.1093/emboj/20.5.1134 .
PMC
145468 .
PMID
11230136 .
Martînez J, Ren YG, Nilsson P, Ehrenberg M, Virtanen A (July 2001).
"The mRNA cap structure stimulates rate of poly(A) removal and amplifies processivity of degradation" . The Journal of Biological Chemistry . 276 (30): 27923–9.
doi :
10.1074/jbc.M102270200 .
PMID
11359775 .
Copeland PR, Wormington M (June 2001).
"The mechanism and regulation of deadenylation: identification and characterization of Xenopus PARN" . RNA . 7 (6): 875–86.
doi :
10.1017/S1355838201010020 .
PMC
1370141 .
PMID
11424938 .
Chen CY, Gherzi R, Ong SE, Chan EL, Raijmakers R, Pruijn GJ, Stoecklin G, Moroni C, Mann M, Karin M (November 2001).
"AU binding proteins recruit the exosome to degrade ARE-containing mRNAs" . Cell . 107 (4): 451–64.
doi :
10.1016/S0092-8674(01)00578-5 .
PMID
11719186 .
S2CID
14817671 .
Ren YG, Martínez J, Virtanen A (February 2002).
"Identification of the active site of poly(A)-specific ribonuclease by site-directed mutagenesis and Fe(2+)-mediated cleavage" . The Journal of Biological Chemistry . 277 (8): 5982–7.
doi :
10.1074/jbc.M111515200 .
PMID
11742007 .
Andersen JS, Lyon CE, Fox AH, Leung AK, Lam YW, Steen H, Mann M, Lamond AI (January 2002).
"Directed proteomic analysis of the human nucleolus" . Current Biology . 12 (1): 1–11.
Bibcode :
2002CBio...12....1A .
doi :
10.1016/S0960-9822(01)00650-9 .
PMID
11790298 .
S2CID
14132033 .
Scherl A, Couté Y, Déon C, Callé A, Kindbeiter K, Sanchez JC, Greco A, Hochstrasser D, Diaz JJ (November 2002).
"Functional proteomic analysis of human nucleolus" . Molecular Biology of the Cell . 13 (11): 4100–9.
doi :
10.1091/mbc.E02-05-0271 .
PMC
133617 .
PMID
12429849 .
Lai WS, Kennington EA, Blackshear PJ (June 2003).
"Tristetraprolin and its family members can promote the cell-free deadenylation of AU-rich element-containing mRNAs by poly(A) ribonuclease" . Molecular and Cellular Biology . 23 (11): 3798–812.
doi :
10.1128/MCB.23.11.3798-3812.2003 .
PMC
155217 .
PMID
12748283 .
Lejeune F, Li X, Maquat LE (September 2003).
"Nonsense-mediated mRNA decay in mammalian cells involves decapping, deadenylating, and exonucleolytic activities" . Molecular Cell . 12 (3): 675–87.
doi :
10.1016/S1097-2765(03)00349-6 .
PMID
14527413 .
Gherzi R, Lee KY, Briata P, Wegmüller D, Moroni C, Karin M, Chen CY (June 2004).
"A KH domain RNA binding protein, KSRP, promotes ARE-directed mRNA turnover by recruiting the degradation machinery" . Molecular Cell . 14 (5): 571–83.
doi :
10.1016/j.molcel.2004.05.002 .
PMID
15175153 .
Lehner B, Sanderson CM (July 2004).
"A protein interaction framework for human mRNA degradation" . Genome Research . 14 (7): 1315–23.
doi :
10.1101/gr.2122004 .
PMC
442147 .
PMID
15231747 .
Ren YG, Kirsebom LA, Virtanen A (November 2004).
"Coordination of divalent metal ions in the active site of poly(A)-specific ribonuclease" . The Journal of Biological Chemistry . 279 (47): 48702–6.
doi :
10.1074/jbc.M403858200 .
PMID
15358788 .
PDB gallery
1whv : Solution structure of the RNA binding domain from hypothetical protein BAB23382
2a1r : Crystal structure of PARN nuclease domain
2a1s : Crystal structure of native PARN nuclease domain
Activity Regulation Classification Kinetics Types
Type I
ALK1 (
ACVRL1 )
ALK2 (
ACVR1A )
ALK3 (
BMPR1A )
ALK4 (
ACVR1B )
ALK5 (
TGFβR1 )
ALK6 (
BMPR1B )
Agonists:
BMP (
2 ,
4 ,
5 ,
6 ,
7 ,
8A ,
8B ,
15 (GDF9B) )
Dibotermin alfa
Eptotermin alfa
GDF (
5 (BMP14) ,
6 (BMP13) ,
7 (BMP12) ,
9 ,
15 )
Radotermin
ALK7 (
ACVR1C )
Type II
TGFβR2
BMPR2
ACVR2A (
ACVR2 )
Agonists:
Activin (
A ,
B ,
AB )
BMP (
2 ,
4 ,
5 ,
6 ,
7 ,
8A ,
8B ,
15 (GDF9B) )
Dibotermin alfa
Eptotermin alfa
GDF (
1 ,
3 ,
5 (BMP14) ,
6 (BMP13) ,
7 (BMP12) ,
9 ,
11 (BMP11) ,
15 )
Myostatin (GDF8)
Nodal
Radotermin
ACVR2B
Agonists:
Activin (
A ,
B ,
AB )
BMP (
2 ,
4 ,
6 ,
7 )
Dibotermin alfa
Eptotermin alfa
GDF (
1 ,
3 ,
5 (BMP14) ,
6 (BMP13) ,
7 (BMP12) )
Myostatin (GDF8)
Nodal
Osteogenin (BMP3, BMP3A)
Radotermin
AMHR2 (
AMHR )
Type III
Unsorted