Journal article
The novel poly(A) polymerase Star-PAP is a signal-regulated switch at the 3′-end of mRNAs
Advances in biological regulation, Vol.53(1), pp.64-76
01/2013
Handle:
https://hdl.handle.net/2376/110780
PMCID: PMC3626085
PMID: 23306079
Abstract
The mRNA 3′-untranslated region (3′-UTR) modulates message stability, transport, intracellular location and translation. We have discovered a novel nuclear poly(A) polymerase termed Star-PAP (nuclear speckle targeted PIPKIα regulated-poly(A) polymerase) that couples with the transcriptional machinery and is regulated by the phosphoinositide lipid messenger phosphatidylinositol-4,5-bisphosphate (PI4,5P2), the central lipid in phosphoinositide signaling. PI4,5P2 is generated primarily by type I phosphatidylinositol phosphate kinases (PIPKI). Phosphoinositides are present in the nucleus including at nuclear speckles compartments separate from known membrane structures. PIPKs regulate cellular functions by interacting with PI4,5P2 effectors where PIPKs generate PI4,5P2 that then modulates the activity of the associated effectors. Nuclear PIPKIα interacts with and regulates Star-PAP, and PI4,5P2 specifically activates Star-PAP in a gene- and signaling-dependent manner. Importantly, other select signaling molecules integrated into the Star-PAP complex seem to regulate Star-PAP activities and processivities toward RNA substrates, and unique sequence elements around the Star-PAP binding sites within the 3′-UTR of target genes contribute to Star-PAP specificity for processing. Therefore, Star-PAP and its regulatory molecules form a signaling nexus at the 3′-end of target mRNAs to control the expression of select group of genes including the ones involved in stress responses.
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Details
- Title
- The novel poly(A) polymerase Star-PAP is a signal-regulated switch at the 3′-end of mRNAs
- Creators
- Weimin Li - University of Wisconsin–Madison, School of Medicine and Public Health, Medical Sciences Center, 1300 University Ave., Madison, WI 53706, USARakesh S Laishram - Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Trivandrum 695014, IndiaRichard A Anderson - University of Wisconsin–Madison, School of Medicine and Public Health, Medical Sciences Center, 1300 University Ave., Madison, WI 53706, USA
- Publication Details
- Advances in biological regulation, Vol.53(1), pp.64-76
- Academic Unit
- Biomedical Sciences, Department of
- Publisher
- Elsevier Ltd
- Identifiers
- 99900547222101842
- Language
- English
- Resource Type
- Journal article