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Pumilio homolog 2

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) (, PubMed:21397187). 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. Acts as a post-transcriptional repressor of E2F3 mRNAs by binding to its 3'-UTR and facilitating miRNA regulation. Plays a role in cytoplasmic sensing of viral infection. 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. May regulate DCUN1D3 mRNA levels. May support proliferation and self-renewal of stem cells. Binds specifically to miRNA MIR199A precursor, with PUM1, 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]. 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]

[4]. 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]

[5]. 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]

[6]. Guochang Huang, et al. SCCRO3 (DCUN1D3) antagonizes the neddylation and oncogenic activity of SCCRO (DCUN1D1). J Biol Chem. 2014 Dec 12;289(50):34728-42. [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]. 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]

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