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(Circulation Research. 2007;100:761.)
© 2007 American Heart Association, Inc.

Editorials

One Gene, Many Proteins

Alternative Splicing of the Ryanodine Receptor Gene Adds Novel Functions to an Already Complex Channel Protein

Héctor H. Valdivia

From the Department of Physiology, University of Wisconsin Medical School.

Correspondence to Héctor H. Valdivia, MD, PhD, Department of Physiology, University of Wisconsin Medical School, 601 Science Dr. Madison, WI 53711. E-mail valdivia@physiology.wisc.edu

See related article, pages 874–883

Key Words: ryanodine receptor • alternative splicing • excitation-contraction coupling • apoptosis

An extract of the first 250 words of the full text is provided, because this article has no abstract.

When the human genome sequence was first drafted in 2000, researchers were shocked by the low number of genes found. Humans make 90 000 different types of protein, so estimates were that at least a similar number of genes would be found. The logic was that, given the structural and functional complexity of the human body, we ought to have more genes than the simpler corn (zea mays, 40 000 genes) or the puny worm Caenorhabditis elegans (19 500 genes). So, when the final number of human genes was established to be fewer than 25 000, researchers immediately realized the gene:protein mismatch, reaffirmed the notion that the axiom "one gene, one protein" was inaccurate, and began looking for the evolutionary mechanisms that increase diversity and complexity from a relatively simple genetic makeup. The answer, it seems, is alternative gene splicing.

When a segment of DNA (gene) is transcribed, the resulting RNA (tRNA) contains meaningful (exons) and nonmeaningful (introns) sequences that must be edited to produce a coherent message (mRNA). This cut-and-paste process where exons are retained and introns are discarded is called gene splicing and constitutes the normal processing of genes. However, as it was first discovered some 25 years ago,¹ "alternative splicing" occurs, a highly regulated process that confers sophistication to the manufacturing of proteins by frequently "violating the rules" and leaving pieces of introns or excising parts of exons in the final mRNA. The resultant protein, a splice variant, thus contains segment(s) of distinct amino . . . [Full Text of this Article]

Related Article:

Alternative Splicing of Ryanodine Receptors Modulates Cardiomyocyte Ca²⁺ Signaling and Susceptibility to Apoptosis

Christopher H. George, Sarah A. Rogers, Benedicte M.A. Bertrand, Richard E.A. Tunwell, N. Lowri Thomas, Derek S. Steele, Eryl V. Cox, Christopher Pepper, Carolyn J. Hazeel, William C. Claycomb, and F. Anthony Lai
Circ. Res. 2007 100: 874-883. [Abstract] [Full Text] [PDF]

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