title: Functional Integration of mRNA Translational Control Programs.
abstract: Regulated mRNA translation plays a key role in control of cell cycle progression in a variety of physiological and pathological processes, including in the self-renewal and survival of stem cells and cancer stem cells. While targeting mRNA translation presents an attractive strategy for control of aberrant cell cycle progression, mRNA translation is an underdeveloped therapeutic target. Regulated mRNAs are typically controlled through interaction with multiple RNA binding proteins (RBPs) but the mechanisms by which the functions of distinct RBPs bound to a common target mRNA are coordinated are poorly understood. The challenge now is to gain insight into these mechanisms of coordination and to identify the molecular mediators that integrate multiple, often conflicting, inputs. A first step includes the identification of altered mRNA ribonucleoprotein complex components that assemble on mRNAs bound by multiple, distinct RBPs compared to those recruited by individual RBPs. This review builds upon our knowledge of combinatorial control of mRNA translation during the maturation of oocytes from Xenopus laevis, to address molecular strategies that may mediate RBP diplomacy and conflict resolution for coordinated control of mRNA translational output. Continued study of regulated ribonucleoprotein complex dynamics promises valuable new insights into mRNA translational control and may suggest novel therapeutic strategies for the treatment of disease.
authors.affiliation: Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Mel@UAMS.edu.|Center for Translational Neuroscience, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Mel@UAMS.edu.
authors.forename: Melanie C
authors.initials: MC
authors.lastname: MacNicol
authors.affiliation: Interdisciplinary BioSciences Graduate Program, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. CCragle@uams.edu.
authors.forename: Chad E
authors.initials: CE
authors.lastname: Cragle
authors.affiliation: Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Karthik.Arumugam@crg.eu.
authors.forename: Karthik
authors.initials: K
authors.lastname: Arumugam
authors.affiliation: Institute of Biomembranes and Bioenergetics, National Research Council, Bari 70126, Italy. bruno.fosso@gmail.com.
authors.forename: Bruno
authors.initials: B
authors.lastname: Fosso
authors.affiliation: Institute of Biomembranes and Bioenergetics, National Research Council, Bari 70126, Italy. bruno.fosso@gmail.com.|Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, Bari 70125, Italy. bruno.fosso@gmail.com.
authors.forename: Graziano
authors.initials: G
authors.lastname: Pesole
authors.affiliation: Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Angus@UAMS.edu.|Center for Translational Neuroscience, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Angus@UAMS.edu.|Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Angus@UAMS.edu.|Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Angus@UAMS.edu.
authors.forename: Angus M
authors.initials: AM
authors.lastname: MacNicol
mesh_terms: D000818:Animals; D002453:Cell Cycle; D006801:Humans; D058990:Molecular Targeted Therapy; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins / Q000378:metabolism
chemical_list: D016601:RNA-Binding Proteins
keywords: CPEB; Musashi; RNA-binding protein; combinatorial control; mRNA translation; mRNP; regulation