A Closer Look at Polyadenylation

Anatolios Georg Buckley (Editor)

Series: Biochemistry Research Trends
BISAC: MED107000

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Edited by I Leslie Rubin, Robert J Geller, Abby Mutic, Benjamin A Gitterman, Nathan Mutic, Wayne Garfinkel, Claire D Coles, Kurt Martinuzzi, and Joav Merrick

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In response to various environmental cues and cellular stress, cells need to modify their protein expression pattern for proper cell functioning. The cell experiences diverse cellular stress as oxidative, genotoxic, and etc. The damage of the genome by certain chemicals or agents affects the cell integrity and leads to genotoxic stress. As such, this compilation discusses how different cellular stresses affect the polyadenylation process and modulate the polyadenylation machinery.

Cytoplasmic polyadenylation plays an important role in oocyte maturation, mitotic cell cycle progression, cellular senescence and synaptic plasticity. Poly(A) tails can be elongated post-transcriptionally by noncanonical poly(A) polymerases, which can impact cells with limited transcriptional activity.

A recent study is discussed wherein it is shown that that alternative cleavage and polyadenylation isoform expression influences about 10% of targeting by miRNAs between any two cell types analysed and, more importantly, that the accuracy of target prediction can be improved if the cellular alternative cleavage and polyadenylation profile is considered.

The authors go on to focus on how altering the polyadenylation process and components of RNA polyadenylation machinery leads to abnormal physiological conditions. The targeting of elements of RNA polyadenylation machinery as therapeutics in clinical research is also discussed.

The majority of eukaryotic mRNAs are polyadenylated at their 3´end. This poly(A) tail is not encoded by DNA and is added co-transcriptionally. Cleavage and polyadenylation specific factor (CPSF1) is part of multiple subunit factors required for a site-specific cleavage, which is involved in determining specificity and efficency of the 3´ end processing of pre-mRNAs in the nucleus by recognizing the polyadenylation signal.

Following this, mutations in the poly(A) signal (AAUAAA hexamer) present in the globin pre-mRNA were identified in hematological disorders caused by defects in the synthesis of one or more of the globin chains (thalassemia). The point mutation AATAAA to AACAAA of a human β-globin gene detected in 1985 in DNA from a patient with β-thalassemia led to the formation of an elongated β-globin mRNA isoform.

This compilation addresses how RNA processing at the pre-mRNA level occurs in the cell nucleus and regulates gene expression. Newly synthesized mRNA contains a poly(A) tail, which is added through canonical polyadenylation coupled to transcription. Canonical mRNA 3´ processing involves endonucleolytic cleavage within the pre-mRNA sequences and the addition of a poly(A) tail to the upstream cleavage fragment.

The closing chapter discusses how the poly(A) tail at the 3´end of the majority of eukaryotic messenger RNAs (mRNAs), with the exception of histone transcripts, is not simply a static entity but more likely a dynamic matter. Its length added to an mRNA is regulated by the concerted action of poly(A) polymerases and deadenylases.
(Imprint: Nova)

Preface

Chapter 1. Cellular Stress and Polyadenylation
(Nikhat Saleem and Buddhi Prakash Jain, School of Life Sciences, Jawaharlal Nehru University, New Mehrauli Road, New Delhi, India, and others)

Chapter 2. Cytoplasmic Polyadenylation and Translational Control
(Ota Fuchs, Institute of Hematology and Blood Transfusion, Prague, Czech Republic)

Chapter 3. Alternative Cleavage and Polyadenylation of mRNA and the Effect on microRNAs and Translation
(Ota Fuchs, Institute of Hematology and Blood Transfusion, Prague, Czech Republic)

Chapter 4. Implication of Alteration in RNA Polyadenylation Machinery in Diseases
(Shweta Pandey and Buddhi Prakash Jain, Govt. V.Y.T. PG Autonomous College, Chhattisgarh, India, and others)

Chapter 5. Targeting the Cleavage Factor and Polyadenylation Signal of Pre-mRNA as Methods for Silencing the Causative Gene of the Disease
(Ota Fuchs, Institute of Hematology and Blood Transfusion, Prague, Czech Republic)

Chapter 6. Abnormal Polyadenylation in Diseases
(Ota Fuchs, Institute of Hematology and Blood Transfusion, Prague, Czech Republic)

Chapter 7. The Role of Poly(A) Tails on the 3´ End of mRNA in the Translocation of Processed mRNA from the Nucleus to the Cytoplasm: mRNA Quality Control and Degradation in the Translational Efficiency of mRNA
(Ota Fuchs, Institute of Hematology and Blood Transfusion, Prague, Czech Republic)

Chapter 8. Nuclear and Cytoplasmic Factors that Regulate the Poly(A) Tail Size Dynamics
(Ota Fuchs, Institute of Hematology and Blood Transfusion, Prague, Czech Republic)

Index

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