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Pumilio homolog 1

Definition:

Sequence-specific RNA-binding protein that acts as a post-transcriptional repressor by binding the 3'-UTR of mRNA targets. Binds to an RNA consensus sequence, the Pumilio Response Element (PRE), 5'-UGUANAUA-3', that is related to the Nanos Response Element (NRE). Mediates post-transcriptional repression of transcripts via different mechanisms: acts via direct recruitment of the CCR4-POP2-NOT deadenylase leading to translational inhibition and mRNA degradation. Also mediates deadenylation-independent repression by promoting accessibility of miRNAs. Following growth factor stimulation, phosphorylated and binds to the 3'-UTR of CDKN1B/p27 mRNA, inducing a local conformational change that exposes miRNA-binding sites, promoting association of miR-221 and miR-222, efficient suppression of CDKN1B/p27 expression, and rapid entry to the cell cycle. Acts as a post-transcriptional repressor of E2F3 mRNAs by binding to its 3'-UTR and facilitating miRNA regulation. Represses a program of genes necessary to maintain genomic stability such as key mitotic, DNA repair and DNA replication factors. Its ability to repress those target mRNAs is regulated by the lncRNA NORAD (non-coding RNA activated by DNA damage) which, due to its high abundance and multitude of PUMILIO binding sites, is able to sequester a significant fraction of PUM1 and PUM2 in the cytoplasm. Involved in neuronal functions by regulating ATXN1 mRNA levels: acts by binding to the 3'-UTR of ATXN1 transcripts, leading to their down-regulation independently of the miRNA machinery. Plays a role in cytoplasmic sensing of viral infection. In testis, acts as a post-transcriptional regulator of spermatogenesis by binding to the 3'-UTR of mRNAs coding for regulators of p53/TP53. Involved in embryonic stem cell renewal by facilitating the exit from the ground state: acts by targeting mRNAs coding for naive pluripotency transcription factors and accelerates their down-regulation at the onset of differentiation (By similarity). Binds specifically to miRNA MIR199A precursor, with PUM2, regulates miRNA MIR199A expression at a postranscriptional level.

References:

[1]. Wayne O Miles, et al. Pumilio facilitates miRNA regulation of the E2F3 oncogene. Genes Dev. 2012 Feb 15;26(4):356-68. [Content Brief]

[2]. Gang Lu, et al. Alternate modes of cognate RNA recognition by human PUMILIO proteins. Structure. 2011 Mar 9;19(3):361-7. [Content Brief]

[3]. Aleksandra Filipovska, et al. A universal code for RNA recognition by PUF proteins. Nat Chem Biol. 2011 May 15;7(7):425-7. [Content Brief]

[4]. Sungyul Lee, et al. Noncoding RNA NORAD Regulates Genomic Stability by Sequestering PUMILIO Proteins. Cell. 2016 Jan 14;164(1-2):69-80. [Content Brief]

[5]. Thomas Treiber, et al. A Compendium of RNA-Binding Proteins that Regulate MicroRNA Biogenesis. Mol Cell. 2017 Apr 20;66(2):270-284.e13. [Content Brief]

[6]. Ryo Narita, et al. A novel function of human Pumilio proteins in cytoplasmic sensing of viral infection. PLoS Pathog. 2014 Oct 23;10(10):e1004417. [Content Brief]

[7]. Jamie Van Etten, et al. Human Pumilio proteins recruit multiple deadenylases to efficiently repress messenger RNAs. J Biol Chem. 2012 Oct 19;287(43):36370-83. [Content Brief]

[8]. Martijn Kedde, et al. A Pumilio-induced RNA structure switch in p27-3' UTR controls miR-221 and miR-222 accessibility. Nat Cell Biol. 2010 Oct;12(10):1014-20. [Content Brief]

[9]. Yogesh K Gupta, et al. Structures of human Pumilio with noncognate RNAs reveal molecular mechanisms for binding promiscuity. Structure. 2008 Apr;16(4):549-57. [Content Brief]

[10]. Shuyun Dong, et al. Specific and modular binding code for cytosine recognition in Pumilio/FBF (PUF) RNA-binding domains. J Biol Chem. 2011 Jul 29;286(30):26732-42. [Content Brief]

[11]. Vincenzo A Gennarino, et al. Pumilio1 haploinsufficiency leads to SCA1-like neurodegeneration by increasing wild-type Ataxin1 levels. Cell. 2015 Mar 12;160(6):1087-98. [Content Brief]

[12]. Limor Leibovich, et al. A structural-based statistical approach suggests a cooperative activity of PUM1 and miR-410 in human 3'-untranslated regions. Silence. 2010 Sep 22;1(1):17. [Content Brief]

[13]. Alessia Galgano, et al. Comparative analysis of mRNA targets for human PUF-family proteins suggests extensive interaction with the miRNA regulatory system. PLoS One. 2008 Sep 8;3(9):e3164. [Content Brief]

[14]. Vincenzo A Gennarino, et al. A Mild PUM1 Mutation Is Associated with Adult-Onset Ataxia, whereas Haploinsufficiency Causes Developmental Delay and Seizures. Cell. 2018 Feb 22;172(5):924-936.e11. [Content Brief]

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