Gene Expression and RNA Splicing

The regulation of gene expression is a ubiquitous phenomenon and is involved in virtually every process central to an organism, ranging from the fertilization of germ cells, across the cell cycle, to stimuli–response pathways or apoptosis. To control the expression of genes under such diverse contexts, regulation occurs on different cellular levels and involves a series of complex biochemical mechanisms that one can broadly classify into transcription, RNA processing and cytoplasmic transport, and post-transcriptional control and translation. While a series of distinct machineries is involved in controlling gene expression at each level, these complex circuits bear signs of interconnectedness

In higher eukaryotes, splicing constitutes a critical mode for the regulation of gene expression at the level of RNA processing. The large majority of eukaryotic protein-coding genes are transcribed as precursors of messenger RNAs (pre-mRNAs), in which exons are separated from each other by intervening regions of non-protein–coding information (introns), which have to be correctly spliced out to produce a mature mRNA. Splicing of pre-mRNAs occurs in a two-step reaction. In the first step, the message is cleaved at the 5′ end of an intron, and this 5′ end is linked to the branch point, which is typically in close proximity upstream of the 3′ end of the intron. In the second step, the mRNA intermediate is cleaved at the 3′ splice site (3′ss), exons are ligated, and the intron lariat is released. During later stages of spliceosome assembly, the 5′ss and 3′ss pair and interact (typically across the exon, but pairing across an intron can occur), supported by general and specific splicing factors that recognize them. Typical mammalian genes span tens of thousands of nucleotides, with on average nine exons and protein-coding regions on the order of a thousand nucleotides, thus embedding “exon islands” within a large “sea” of noncoding nucleotides that have to be accurately recognized for correct splicing and exon ligation. This important task is executed in the nucleus by the spliceosome, a large ribonucleoprotein (RNP) complex that involves five small nuclear RNAs and potentially hundreds of proteins, the core components of which are highly conserved across metazoan genomes

Source -http://www.ploscompbiol.org/article/info:doi%2F10.1371%2Fjournal.pcbi.0040021;jsessionid=896ADD2EFF9997239BC16AF2AC45FD6D