Definition: In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
Input: Recent whole genome sequence analyses revealed that a high degree of proteomic complexity is achieved with a limited number of genes. This surprising fi nding underscores the importance of alternative splicing through which a single gene can generate structurally and functionally distinct protein isoforms [ 1 ] . Based on genome-wide analysis, 75% of human genes are thought to encode at least two alternatively spliced isoforms [ 2, 3 ] . The regulation of splice site usage provides a versatile mechanism for controlling gene expression and for the generation of proteome diversity, playing essential roles in many biological processes, such as embryonic development, cell growth, and apoptosis. The splice sites are generally recognized by the splicing machinery, a ribonuclear protein complex known as the spliceosome. Spliceosome binding is determined by competing activities of various auxiliary regulatory proteins, such as members of SR protein or heterogeneous nuclear ribonucleoprotein (hnRNP) families, which bind speci fi c regulatory sequences and alter the binding of the spliceosome to a particular splice site [ 1, 4 ] . Pre-mRNA splicing is regulated in a tissue-speci fi c or developmental stage-speci fi c manner [ 5 ] . The selection of splice site can be altered by numerous extracellular stimuli such as hormones, immune response, neuronal depolarization, and cellular stress, through changes in synthesis/degradation, complex formation, and intracellular localization of regulatory proteins. SR proteins are heavily phosphorylated in cells and involved in constitutive and alternative splicing, and the phosphorylation states of SR proteins are altered in response to these extracellular stimuli [ 6 ] . Splicing mutations located in either intronic or exonic regions frequently cause hereditary diseases, and more than 15% of mutations that cause genetic disease

Introduction Modulation of Pre-mRNA Splicing Patterns with Synthetic Chemicals and Their Clinical Applications