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Alternative_splicing.
Alternative splicing
In eukaryotes the splicing process of a pre-mRNA can lead to different ripe mRNA molecules and therefore to different proteines. This phenomenon is called alternative splicing. Also viruses have adaptated to this biochemical process when using the protein biosynthesis apparatus.
When the pre-mRNA has been transscribed from the DNA, it includes several introns and exons. In Nematodes, the mean is 4-5 exons and introns, in Drosophila there are more than 100 introns and exons in one transscribed pre-mRNA. But what is an intron and what is an exon is not decided yet. This decision is made during the splicing process. The regulation is widely unknown. However, this leads to a new view of genes. A gene therefore is a twofold information structure:
- A DNA sequence coding for the pre-mRNA
- An additional DNA code or other regulating process, which regulates the alternative splicing.
The alternative splicing is of great importance:
- for science, it means that the old idea of one DNA sequence coding for one polypeptide is no longer correct. External information is needed in order to decide which polypeptide is produced, given a DNA sequence and pre-mRNA.
- Since the ways of regulation are inherited, the meaning of mutation must be changed.
- for eukaryotes it was a very important step towards higher efficiency.
- The information can be stored much more economically. Several proteins can be encoded in a DNA sequence whose length would only be enough for two proteins in the prokaryote way of coding.
- It is unnecessary to change the DNA of a gene for the evolution of a new protein. Instead, a new way of regulation can lead to the same effect, but leaving the code for the established proteines unharmed.
- New proteins can evolve much faster than in prokaryotes. Furthermore, they are based on hitherto functional amino acid subchains. This gives a higher probability for a functional new protein.
- Therefore the adaptation to new environments can be much faster - with fewer generations - than in prokaryotes. This might have been one very important step for multicellular organisms with a longer life cycle.
The above article is adapted from from Wikipedia All Wikipedia article text is available under the terms of the GNU Free Documentation License
Regulation of Adenovirus Alternative Pre-Mrna Splicing: Functional Characterization of Exotic and Intronic Splicing Enhancer Elements by Bai-Gong Yue
Regulation of Alternative Splicing (Progress in Molecular and Subcellular Biology, 31) by PH. Jeanteur
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Recent Alternative_splicing related patents
From USPTO:
from PUBMED
1: McNeill L, Cassady RL, Sarkardei S, Cooper JC, Morgan G, Alexander DR.
CD45 isoforms in T cell signalling and development.
Immunol Lett. 2004 Mar 29;92(1-2):125-34.
PMID: 15081536
2: Ebihara S, Yamamoto T, Obata K, Yanagawa Y.
Gene structure and alternative splicing of the mouse glycine transporter
type-2.
Biochem Biophys Res Commun. 2004 May 7;317(3):857-64.
PMID: 15081419
3: Lee SH, Kim TJ, Kim HY, Kim JG, Park MK, Woo KM, Kim SH, Hwang KY, Nam HS,
Min YK, Cho MH.
Expression of the fragile histidine triad gene in normal rat tissues and human
kidney cancer cell lines.
Res Commun Mol Pathol Pharmacol. 2002;112(1-4):145-57.
PMID: 15080505
4: Nakayama EE, Tanaka Y, Nagai Y, Iwamoto A, Shioda T.
A CCR2-V64I polymorphism affects stability of CCR2A isoform.
AIDS. 2004 Apr 12;18(5):729-38.
PMID: 15075507
5: Hayakawa M, Shimazaki Y, Tsushima T, Kato Y, Takano K, Chihara K, Shimatsu
A, Irie M.
Metabolic effects of 20-kilodalton human growth hormone (20K-hGH) for adults
with growth hormone deficiency: results of an exploratory uncontrolled
multicenter clinical trial of 20K-hGH.
J Clin Endocrinol Metab. 2004 Apr;89(4):1562-71.
PMID: 15070913
6: Fischer DC, Noack K, Runnebaum IB, Watermann DO, Kieback DG, Stamm S,
Stickeler E.
Expression of splicing factors in human ovarian cancer.
Oncol Rep. 2004 May;11(5):1085-90.
PMID: 15069551
7: Dauksaite V, Akusjarvi G.
The second RNA binding domain of human splicing factor ASF/SF2 is the critical
domain controlling adenovirus E1A alternative 5' splice site selection.
Biochem J. 2004 Apr 7 [Epub ahead of print]
PMID: 15068396
8: Nicholls CD, Shields MA, Lee PW, Robbins SM, Beattie TL.
UV-dependent alternative splicing uncouples p53 activity and PIG3 gene function
through rapid proteolytic degradation.
J Biol Chem. 2004 Apr 2 [Epub ahead of print]
PMID: 15067011
9: Ranum LP, Day JW.
Myotonic dystrophy: RNA pathogenesis comes into focus.
Am J Hum Genet. 2004 May;74(5):793-804. Epub 2004 Apr 02.
PMID: 15065017
10: Huang X, Wang H, Xu M, Lu L, Xu Z, Li J, Zhou Z, Sha J.
Expression of a Novel RAD23B mRNA Splice Variant in the Human Testis.
J Androl. 2004 May-Jun;25(3):363-8.
PMID: 15064313
11: Chan CB, Cheng CH.
Identification and functional characterization of two alternatively spliced
growth hormone secretagogue receptor transcripts from the pituitary of black
seabream Acanthopagrus schlegeli.
Mol Cell Endocrinol. 2004 Feb 12;214(1-2):81-95.
PMID: 15062547
12: Wang HC, Su YR, Han KJ, Pang XW, Peng JR, Liang B, Wang S, Chen WF.
Multiple variants and a differential splicing pattern of kinectin in human
hepatocellular carcinoma.
Biochem Cell Biol. 2004 Apr;82(2):321-7.
PMID: 15060627
13: Thaler C, Gray AC, Lipscombe D.
Cumulative inactivation of N-type CaV2.2 calcium channels modified by
alternative splicing.
Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5675-9. Epub 2004 Apr 01.
PMID: 15060274
14: Lutsenko EA, Carcamo JM, Golde DW.
A human sodium-dependent vitamin C transporter 2 isoform acts as a
dominant-negative inhibitor of ascorbic acid transport.
Mol Cell Biol. 2004 Apr;24(8):3150-6.
PMID: 15060139
15: Kvam TM, Baar C, Rakvag TT, Kaasa S, Krokan HE, Skorpen F.
Genetic analysis of the murine micro opioid receptor: increased complexity of
Oprm gene splicing.
J Mol Med. 2004 Apr;82(4):250-5. Epub 2004 Jan 09.
PMID: 14991152
16: Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U,
Goodstein D, Couronne O, Tran-Gyamfi M, Aerts A, Altherr M, Ashworth L, Bajorek
E, Black S, Branscomb E, Caenepeel S, Carrano A, Caoile C, Chan YM, Christensen
M, Cleland CA, Copeland A, Dalin E, Dehal P, Denys M, Detter JC, Escobar J,
Flowers D, Fotopulos D, Garcia C, Georgescu AM, Glavina T, Gomez M, Gonzales E,
Groza M, Hammon N, Hawkins T, Haydu L, Ho I, Huang W, Israni S, Jett J, Kadner
K, Kimball H, Kobayashi A, Larionov V, Leem SH, Lopez F, Lou Y, Lowry S,
Malfatti S, Martinez D, McCready P, Medina C, Morgan J, Nelson K, Nolan M,
Ovcharenko I, Pitluck S, Pollard M, Popkie AP, Predki P, Quan G, Ramirez L, Rash
S, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, She X, Smith D,
Slezak T, Solovyev V, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wagner M,
Wheeler J, Wu K, Xie G, Yang J, Dubchak I, Furey TS, DeJong P, Dickson M, Gordon
D, Eichler EE, Pennacchio LA, Richardson P, Stubbs L, Rokhsar DS, Myers RM,
Rubin EM, Lucas SM.
The DNA sequence and biology of human chromosome 19.
Nature. 2004 Apr 1;428(6982):529-35.
PMID: 15057824
17: Winter J, Lehmann T, Krauss S, Trockenbacher A, Kijas Z, Foerster J, Suckow
V, Yaspo ML, Kulozik A, Kalscheuer V, Schneider R, Schweiger S.
Regulation of the MID1 protein function is fine-tuned by a complex pattern of
alternative splicing.
Hum Genet. 2004 Mar 31 [Epub ahead of print]
PMID: 15057556
18: Katyal S, Godbout R.
Alternative splicing modulates Disabled-1 (Dab1) function in the developing
chick retina.
EMBO J. 2004 Apr 1 [Epub ahead of print]
PMID: 15057276
19: Furlow JD, Yang H, Hsu M, Lim W, Ermio DJ, Chiellini G, Scanlan TS.
Induction of larval tissue resorption in Xenopus laevis tadpoles by the thyroid
hormone receptor agonist GC-1.
J Biol Chem. 2004 Mar 30 [Epub ahead of print]
PMID: 15056670
20: McAlinden A, Havlioglu N, Sandell LJ.
Regulation of protein diversity by alternative pre-mRNA splicing with specific
focus on chondrogenesis.
Birth Defects Res Part C Embryo Today. 2004 Mar;72(1):51-68.
PMID: 15054904
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