Mechanisms and Regulation of Alternative Pre-mRNA Splicing

Annual Review of Biochemistry
Yeon Lee, Donald C Rio

Abstract

Precursor messenger RNA (pre-mRNA) splicing is a critical step in the posttranscriptional regulation of gene expression, providing significant expansion of the functional proteome of eukaryotic organisms with limited gene numbers. Split eukaryotic genes contain intervening sequences or introns disrupting protein-coding exons, and intron removal occurs by repeated assembly of a large and highly dynamic ribonucleoprotein complex termed the spliceosome, which is composed of five small nuclear ribonucleoprotein particles, U1, U2, U4/U6, and U5. Biochemical studies over the past 10 years have allowed the isolation as well as compositional, functional, and structural analysis of splicing complexes at distinct stages along the spliceosome cycle. The average human gene contains eight exons and seven introns, producing an average of three or more alternatively spliced mRNA isoforms. Recent high-throughput sequencing studies indicate that 100% of human genes produce at least two alternative mRNA isoforms. Mechanisms of alternative splicing include RNA-protein interactions of splicing factors with regulatory sites termed silencers or enhancers, RNA-RNA base-pairing interactions, or chromatin-based effects that can change or determine spli...Continue Reading

References

Dec 1, 1989·Genes & Development·P FabrizioJ Abelson
Jun 17, 1994·Cell·P A Sharp
Jan 15, 1996·Genes & Development·H LouS M Berget
Aug 21, 1997·Nature·E J SontheimerJ A Piccirilli
Sep 17, 1998·Nature·Y Hirose, J L Manley
May 27, 1999·Genes & Development·Y HiroseJ L Manley
Jul 16, 1999·The EMBO Journal·M CaputiA M Zahler
Jan 11, 2000·Molecular and Cellular Biology·H X LiuA R Krainer
Oct 19, 2001·Nature·S Valadkhan, J L Manley
Apr 23, 2002·Nature Reviews. Genetics·Luca CartegniAdrian R Krainer
Jul 13, 2002·Science·William G FairbrotherChristopher B Burge
Sep 7, 2002·Proceedings of the National Academy of Sciences of the United States of America·Zhaolan ZhouRobin Reed
Sep 13, 2002·Nature·Zhaolan ZhouRobin Reed
Nov 15, 2002·Methods : a Companion to Methods in Enzymology·Melissa S Jurica, Melissa J Moore
Jan 14, 2003·Nature Structural Biology·Luca Cartegni, Adrian R Krainer
Mar 11, 2003·Annual Review of Biochemistry·Douglas L Black
Jun 18, 2003·RNA·Saba Valadkhan, James L Manley
Jul 2, 2003·Nature Genetics·Tsuyoshi Kashima, James L Manley
Jul 31, 2003·Molecular Cell·Melissa S Jurica, Melissa J Moore
Oct 11, 2003·Molecular Cell·Manuel de la MataAlberto R Kornblihtt
Nov 15, 2003·Science·Jernej UleRobert B Darnell
Feb 26, 2004·Nature Structural & Molecular Biology·Melissa S JuricaNikolaus Grigorieff
Apr 21, 2004·Nature Structural & Molecular Biology·Daniel BoehringerHolger Stark

❮ Previous
Next ❯

Citations

Nov 4, 2015·Biomolecules·Lulzim Shkreta, Benoit Chabot
Feb 21, 2016·Pharmacology & Therapeutics·Susumu OhyaKatsuhiko Muraki
Aug 21, 2015·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Jessica A WarnsArchana Dhasarathy
Jan 6, 2016·The Journal of Cell Biology·Benoit Chabot, Lulzim Shkreta
Dec 25, 2015·Trends in Molecular Medicine·Maayan Salton, Tom Misteli
Oct 31, 2015·Fungal Genetics and Biology : FG & B·Norbert ÁgErzsébet Fekete
Dec 3, 2015·European Journal of Endocrinology·Jonàs Juan-MateuDécio L Eizirik
Sep 8, 2015·The Journal of Nutritional Biochemistry·Amanda J Bird
Mar 26, 2016·Science·Jamie H D Cate
Mar 31, 2016·Wiley Interdisciplinary Reviews. RNA·Sheng-Rui LiuJin-Zhi Zhang
Nov 26, 2015·Biosensors & Bioelectronics·César S HuertasL M Lechuga
Aug 12, 2015·Nucleic Acids Research·Nicholas StepankiwJeffrey A Pleiss
Jul 8, 2015·Genome Biology·Daniel Dominguez, Christopher B Burge
Apr 27, 2016·Proceedings of the National Academy of Sciences of the United States of America·Qingqing WangDonald C Rio
May 11, 2016·Nature Communications·Philippe JulienBen Lehner
Jun 2, 2016·DNA Repair·Brian MagnusonMats Ljungman
Jun 12, 2016·Nucleic Acids Research·Mallory A Havens, Michelle L Hastings
Jul 29, 2016·Wiley Interdisciplinary Reviews. RNA·Ruth Sperling
Jul 28, 2016·RNA Biology·Chien-Ling LinWilliam G Fairbrother
Aug 6, 2016·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Koichi YamamotoKunio Inoue
Aug 26, 2016·Nucleic Acids Research·Julia C OddoEric T Wang
Sep 16, 2016·Current Genetics·Benjamin Jung Fair, Jeffrey A Pleiss
Oct 22, 2016·Trends in Genetics : TIG·Volker Boehm, Niels H Gehring
Oct 16, 2016·Blood Cancer Journal·A BonizzatoS Bortoluzzi
Nov 11, 2016·BioMed Research International·Mirsha Pamela Hernández-RiveraOmar Hernández-Montes
Oct 30, 2016·RNA Biology·Schraga Schwartz, Yuri Motorin
Nov 3, 2016·Expert Opinion on Biological Therapy·S FletcherS D Wilton
Apr 23, 2016·PloS One·Dena LeshkowitzShirley Horn-Saban

❮ Previous
Next ❯

Methods Mentioned

BETA
RNA-seq
electron microscopy
antisense oligonucleotides
affinity purification
gel
electrophoresis
electron
X-ray
fluorescence resonance
exome-sequencing

Software Mentioned

Ensembl
CoSMoS

Related Concepts

Related Feeds

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

ALS: Genetics

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. ALS is a genetically heterogeneous disorder with several causative genes. Here are the latest discoveries pertaining to the genetics of this disease.

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.

B-Cell Leukemia (Keystone)

B-cell leukemia includes various types of lymphoid leukemia that affect B cells. Here is the latest research on B-cell leukemia.

Cancer -Omics

A variety of different high-throughput technologies can be used to identify the complete catalog of changes that characterize the molecular profile of cohorts of tumor samples. Discover the latest insights gained from cancer 'omics' in this feed.

Anthelmintics (ASM)

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.

CRISPR for Genome Editing

Genome editing technologies enable the editing of genes to create or correct mutations. Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). Here is the latest research on the use of CRISPR-Cas system in gene editing.

CRISPR in Cancer

CRISPR-Cas system enables the editing of genes to create or correct mutations. Given that genome instability and mutation is one of the hallmarks of cancer, the CRISPR-Cas system is being explored to genetically alter and eliminate cancer cells. Here is the latest research.

CZI Human Cell Atlas Seed Network

The aim of the Human Cell Atlas (HCA) is to build reference maps of all human cells in order to enhance our understanding of health and disease. The Seed Networks for the HCA project aims to bring together collaborators with different areas of expertise in order to facilitate the development of the HCA. Find the latest research from members of the HCA Seed Networks here.

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.

ALS: Pathogenic Mechanisms

Amyotrophic Lateral Sclerosis is a progressive neurodegenerative disorder characterized by muscle weakness. Here is the latest research investigating pathogenic mechanisms that underlie this genetically heterogeneous disorder.

Amyloid Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive nervous system disease associated with the death of neurons that control voluntary muscles. Discover the latest research on ALS here.

ALS: Phenotypes

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder characterized phenotypically by progressive muscle weakness. Clinical phenotypes of ALS can be classified based on the pattern, level, and area of onset (e.g. bulbar, cervical, lumbar). Here is the latest research investigating phenotypes of ALS.

ALS & FTD: TDP-43

TAR DNA-binding protein 43 (TDP-43) is a pathological protein identified in sporadic Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). Here are the latest discoveries pertaining to TDP-43 and these diseases.

CRISPR Ribonucleases Deactivation

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on mechanisms that underlie deactivation of CRISPR ribonucleases. Here is the latest research.

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

ALS: Genetics

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. Here is the latest research investigating genetic alterations in this genetically heterogeneous disorder.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.