MadSci Network: Molecular Biology

RE: 2 different mRNA sizes for one gene

Area: Molecular Biology
Posted By: Michael Onken, WashU
Date: Wed Oct 30 18:08:02 1996

My question is: are both of the RNA species detected true
messenger RNA? Or is one of them (presumably the one with
higher molecular weight)an unprocessed, or immature, mRNA
that undergoes further processing into a more translatable

There are several genes that produce two or more different sizes of mRNA by a mechanism called alternative splicing. As the name implies, alternative splicing involves changes in the way that the nascent hnRNA (heteronuclear RNA)is processed.

After transcription, a message must be processed before entering the cytoplasm for translation: a 5'-5' 7-methyl-Guanidine cap must be added to the front (5' end); a poly-Adenine tail must be added to the back (3' end); and all of the introns (non-coding regions that make up most of the hnRNA) must be spliced out of the middle. A complex machinery of RNA-based enzymes (small nuclear RiboNuclear Particles, snRNP's, pronounced, "snirps") recognizes where the exons (coding regions between introns) begin and end, and pulls the ends together while removing the intervening introns.

Sometimes, the sites used by the snRNP's to find exons can be masked, such that an exon is treated as part of the flanking introns, and never spliced back into the message. In many genes, this loss of an exon is strictly controled by various factors, so that a single gene can produce two (or sometimes more) messages of different lengths, which in turn can produce similar proteins with different activities.

You mentioned collagen, so I will use a related example closer to my work: Fibronectin is a protein excreted by cells to form part of the extracellular matrices such as connective tissue, basement membranes, etc. There are 20 forms of fibronectin in humans, all arising from a single gene. This is relevant, because one of the exons that is alternatively spliced out of fibronectin codes for a recognition site that is necessary for some cells to bind to fibronectin. Because fibronectin appears to play an important role in development, it has been postulated that alternative splice forms of fibronectin may create a "road map" to tell different cells where to go to make an embryo.

Dr. Phillip Sharp won the Nobel Prize in Medicine for his work on mRNA splicing, and I know he has written several reviews on the subject, if you are interested in more information.

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