Mechanisms of Post-transcriptional Gene Regulation
Post-transcriptional control plays a pervasive role in the regulation of gene expression, with direct relevance to the proper function of endocrine systems. This chapter explores the mechanisms that control protein expression at the levels of translation
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Mechanisms of Post-transcriptional Gene Regulation René Arvola, Elizabeth Abshire, Jennifer Bohn, and Aaron C. Goldstrohm
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Introduction
Gene expression involves multiple sequential steps which are highly regulated and coordinated. Regulation of gene expression is crucial for proper function of the endocrine system. Over the past several decades, an abundance of data has accumulated which demonstrates the importance of post-transcriptional mechanisms in control of the endocrine function, which is the subject of this book. These mechanisms can control the amount, timing, and location of protein expression. Moreover, post-transcriptional mechanisms of RNA processing and editing can change the properties of expressed proteins. The purpose of this chapter is to provide an overview of post-transcriptional regulation, focusing on translation and mRNA degradation pathways. We also explore our current knowledge of the mechanisms that regulate protein synthesis and mRNA stability. We refer readers to recent comprehensive reviews on additional post-transcriptional mechanisms including RNA processing (Elkon et al. 2013; Fu and Ares 2014) and modifications (Wang and He 2014), nucleo-cytoplasmic transport (Wickramasinghe and Laskey 2015) and localization (Buxbaum et al. 2015). Opportunities for post-transcriptional control are numerous. Messenger RNAs (mRNAs) contain extensive cis-acting sequences that can control RNA processing, translation efficiency, and mRNA stability. Furthermore, eukaryotic genomes encode a large repertoire of trans-acting regulators, including RNA binding proteins
Note: Due to the space limitations and the broad nature of this chapter, we were unable to cite many important contributions, thus we apologize to colleagues whose work could not be highlighted. R. Arvola • E. Abshire • J. Bohn • A.C. Goldstrohm (*) Department of Biological Chemistry, University of Michigan Medical School, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA e-mail: [email protected] © Springer International Publishing Switzerland 2016 K.M.J. Menon, A.C. Goldstrohm (eds.), Post-transcriptional Mechanisms in Endocrine Regulation, DOI 10.1007/978-3-319-25124-0_1
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and non-coding RNAs, with potential regulatory functions. Current estimates indicate that the human genome encodes some 1500 RNA binding proteins (Gerstberger et al. 2014) and thousands of non-coding RNAs, such as the small regulatory microRNAs (miRNAs) (Bartel 2004; Geisler and Coller 2013). Yet the function of the vast majority of this regulatory potential remains to be explored, especially in physiological systems. The chapters of this volume highlight elegant cases wherein intricate post-transcriptional regulatory mechanisms control responses to and responses from endocrine pathways.
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Translation Regulation
Translation efficiency plays an important role in determining the level of protein expression. Globally, protein levels correlate poorly with mRNA levels, and translation efficiencies of mRNAs vary widely (Schwanhausser et al. 2
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