Genome complexity: alternative splicing (Introduction)

by David Turell @, Tuesday, February 11, 2020, 17:07 (6 days ago) @ David Turell

How do 20,000 +/- genes create many billions of human proteins? through alternative splicing of the genes:

"Seventeen years ago, the completion of the Human Genome Project revealed that there are around 20,000 protein-coding genes in the human genome—a puzzling result, given our intricate biology. Thanks to the advancement of large-scale proteomic studies over the decade following that milestone, researchers realized that some human cells contain billions of different polypeptides. Researchers realized that each gene can encode an array of proteins. The process of alternative splicing, which had first been observed 26 years before the Human Genome Project was finished, allows a cell to generate different RNAs, and ultimately different proteins, from the same gene. Since its discovery, it has become clear that alternative splicing is common and that the phenomenon helps explain how limited numbers of genes can encode organisms of staggering complexity. While fewer than 40 percent of the genes in a fruit fly undergo alternative splicing, more than 90 percent of genes are alternatively spliced in humans. (my bold)

"Astoundingly, some genes can be alternatively spliced to generate up to 38,000 different transcript isoforms, and each of the proteins they produce has a unique function. Like the chapters of a book, coding segments of the genome, known as exons, appear in series, and alternative splicing works by including or leaving out some of these genomic passages. Some chapters are required—that is, they are found in every transcript—and some are optional, so-called alternative exons. The differential splicing of these regions from an RNA transcript creates customized and condensed genetic messages. Molecular editors control the complicated flurry of exon selection by recognizing the chapters needed for a given protein and discarding the others. The final arrangement of exons in a spliced RNA molecule shapes the resulting protein’s structure and function.


"Still, from an evolutionary perspective, the idea of RNA splicing seemed bizarre to some researchers. In September of 2003, the Encyclopedia of DNA Elements (ENCODE) project was launched to identify the functional elements in the human genome, and the effort ignited controversies as to whether introns were genetic “junk” that the cell invested precious energy and resources to transcribe only to trash prior to translation. Alternative splicing gave these seemingly nonfunctional elements an essential role in gene expression, as evidence emerged over the next few years that there are sequences housed within introns that can help or hinder splicing activity. These enhancer and silencer sequences are recognized by RNA-binding proteins (RBPs) whose presence affects spliceosome docking and assembly. The RBPs allow exons or portions of exons to be combined or skipped in unique patterns, such that a single transcript can be spliced into several possible mature mRNA isoforms, or splice variants, each translated into proteins with potentially diverse functions. (My bold)


"While some details of the mechanisms of splicing remain to be worked out, it’s known that mature, edited mRNAs result from an interplay between multiple factors within and outside the transcript itself. Among these is the spliceosome, the machinery that carries out the splicing.


"A variety of factors affect how transcripts from a particular gene are spliced. Exon recognition by the spliceosome can be influenced by RNA binding proteins (RBPs), which bind to enhancer and silencer motifs within the mRNA and help or hinder spliceosome recognition of the splice sites. And because pre-mRNAs are frequently spliced as they’re transcribed, the speed of transcription by RNA polymerase II further tunes the window of opportunity for splice site recognition by the spliceosome."

Comment: We all knew there had to be hidden levels of genome functionality. We see a portion of it in this research as more 'junk' DNA disappears. Anyone who denies that this is designed is not thinking logically. Note how prominent this is in humans compared to fruit flies. Another discovery that shows how special we are.

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