Cellular and Molecular Life Sciences

, Volume 69, Issue 4, pp 501–517

The complex world of post-transcriptional mechanisms: is their deregulation a common link for diseases? Focus on ELAV-like RNA-binding proteins

Review

DOI: 10.1007/s00018-011-0810-7

Cite this article as:
Pascale, A. & Govoni, S. Cell. Mol. Life Sci. (2012) 69: 501. doi:10.1007/s00018-011-0810-7

Abstract

Post-transcriptional mechanisms are key determinants in the modulation of the expression of final gene products. Within this context, fundamental players are RNA-binding proteins (RBPs), and among them ELAV-like proteins. RBPs are able to affect every aspect in the processing of transcripts, from alternative splicing, polyadenylation, and nuclear export to cytoplasmic localization, stability, and translation. Of interest, more than one RBP can bind simultaneously the same mRNA; therefore, since each RBP is endowed with different properties, the balance of these interactions dictates the ultimate fate of the transcript, especially in terms of both stability and rate of translation. Besides RBPs, microRNAs are also important contributors to the post-transcriptional control of gene expression. Within this general context, the present review focuses on ELAV-like proteins describing their roles in the nucleus and in the cytoplasm, also highlighting some examples of interactions with other RBPs and with microRNAs. We also examine the putative role and the observed changes of ELAV-like proteins and of their interactions with other regulatory elements in Alzheimer’s disease, cancer, and inflammation. The changes in the expression of proteins involved in these diseases are examples of how a derangement in the mRNA stabilization process may be associated with disease development and contribute to pathology. Overall, we hope that the topics handled in the present manuscript provide a hint to look at ELAV-like-mediated mRNA stabilization as a mechanism relevant to disease as well as a novel putative drug target.

Keywords

ELAV-like RNA-binding proteinsPost-translational mechanismsmRNA stabilitymiRNAsAlzheimer’s diseaseCancerInflammation

Abbreviations

AAO

Age-at-onset

Beta-amyloid

AD

Alzheimer’s disease

ADAMs

A disintegrin and metalloproteinase

APP

Amyloid precursor protein

ARE

Adenine–uridine-rich elements

ARE-BPs

ARE-binding proteins

CAT-1

Cationic amino acid transporter 1

Dnd1

Dead-end 1

ELAV

Embryonic lethal abnormal vision

GAP-43

Growth-associated protein 43

GM-CSF

Granulocyte-macrophage colony-stimulating factor

IL-1β

Interleukin-1 beta

LNA

Locked nucleic acid

MAPK

Mitogen-activated protein kinase

MI

Myocardial infarction

miRNAs

microRNAs

mRNPs

Messenger ribonucleoprotein particles

MAT

Methionine adenosyltransferase

nELAV-like

Neuronal ELAV-like

NOVA-1

Neuro-oncological ventral antigen-1

NF

Neurofibrillary tangles

NF-kB

Nuclear factor-kappa B

PD

Parkinson’s disease

PKC

Protein kinase C

RBPs

RNA-binding proteins

RISC

RNA-induced silencing complex

RRMs

RNA-recognizing motifs

TNFα

Tumor necrosis factor alpha

TTP

Tristetraprolin

5′-UTR

5′-untranslated region

3′-UTR

3′-untranslated region

VEGF

Vascular endothelial growth factor

Copyright information

© Springer Basel AG 2011

Authors and Affiliations

  1. 1.Section of Pharmacology, Department of Drug SciencesUniversity of PaviaPaviaItaly