Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene may be included within or excluded from the final RNA product of the gene. This means the exons are joined in different combinations, leading to different splice variants. In the case of protein-coding genes, the proteins translated from these splice variants may contain differences in their amino acid sequence and in their biological functions.
Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that exists in all eukaryotes. Its main function is to reduce errors in gene expression by eliminating mRNA transcripts that contain premature stop codons. Translation of these aberrant mRNAs could, in some cases, lead to deleterious gain-of-function or dominant-negative activity of the resulting proteins.
Gideon Dreyfuss is an American biochemist, the Isaac Norris Professor of Biochemistry and Biophysics at the University of Pennsylvania School of Medicine, and an investigator of the Howard Hughes Medical Institute. He was elected to the National Academy of Sciences in 2012.
Nuclear RNA export factor 1, also known as NXF1 or TAP, is a protein which in humans is encoded by the NXF1 gene.
Serine/arginine repetitive matrix protein 1 is a protein that in humans is encoded by the SRRM1 gene.
Splicing factor 3 subunit 1 is a protein that in humans is encoded by the SF3A1 gene.
RNA-binding protein with serine-rich domain 1 is a protein that in humans is encoded by the RNPS1 gene.
Regulator of nonsense transcripts 2 is a protein that in humans is encoded by the UPF2 gene.
Splicing factor, arginine/serine-rich 9, also known as SFRS9, is a human gene encoding an SR protein involved in splice site selection in alternative splicing.
Regulator of nonsense transcripts 3B is a protein that in humans is encoded by the UPF3B gene.
Aly/REF export factor, also known as THO complex subunit 4 is a protein that in humans is encoded by the ALYREF gene.
Protein mago nashi homolog is a human protein encoded by the MAGOH gene. This gene encodes the mammalian homolog of the Drosophila mago nashi gene. In mammals, mRNA expression is not limited to the germplasm, but is ubiquitous in adult tissues and can be induced by serum stimulation of quiescent fibroblasts.
Splicing factor 3B subunit 3 is a protein that in humans is encoded by the SF3B3 gene.
Regulator of nonsense transcripts 3A is a protein that in humans is encoded by the UPF3A gene.
Heterogeneous nuclear ribonucleoprotein R is a protein that in humans is encoded by the HNRNPR gene.
RNA binding motif protein 9 (RBM9), also known as Rbfox2, is a protein which in humans is encoded by the RBM9 gene.
Polypyrimidine tract-binding protein 1 is a protein that in humans is encoded by the PTBP1 gene.
mRNA surveillance mechanisms are pathways utilized by organisms to ensure fidelity and quality of messenger RNA (mRNA) molecules. There are a number of surveillance mechanisms present within cells. These mechanisms function at various steps of the mRNA biogenesis pathway to detect and degrade transcripts that have not properly been processed.
An exon junction complex (EJC) is a protein complex which forms on a pre-messenger RNA strand at the junction of two exons which have been joined together during RNA splicing. The EJC has major influences on translation, surveillance, localization of the spliced mRNA, and m6A methylation. It is first deposited onto mRNA during splicing and is then transported into the cytoplasm. There it plays a major role in post-transcriptional regulation of mRNA. It is believed that exon junction complexes provide a position-specific memory of the splicing event. The EJC consists of a stable heterotetramer core, which serves as a binding platform for other factors necessary for the mRNA pathway. The core of the EJC contains the protein eukaryotic initiation factor 4A-III bound to an adenosine triphosphate (ATP) analog, as well as the additional proteins Magoh and Y14. The binding of these proteins to nuclear speckled domains has been measured recently and it may be regulated by PI3K/AKT/mTOR signaling pathways. In order for the binding of the complex to the mRNA to occur, the eIF4AIII factor is inhibited, stopping the hydrolysis of ATP. This recognizes EJC as an ATP dependent complex. EJC also interacts with a large number of additional proteins; most notably SR proteins. These interactions are suggested to be important for mRNA compaction. The role of EJC in mRNA export is controversial.
The TREX (TRanscription-EXport) complex is a conserved eukaryotic multi-protein complex that couples mRNA transcription and nuclear export. The TREX complex travels across transcribed genes with RNA polymerase II. TREX binds mRNA and recruits transport proteins NXF1 and NXT1, which shuttle the mRNA out of the nucleus. The TREX complex plays an important role in genome stability and neurodegenerative diseases.
