The John Cooper School
Alternative splicing occurs between transcription and translation,
encompassed by a broader process known as pre-mRNA processing. At this stage,
small nuclear ribonucleoprotein particles form spliceosome complexes around
splice sites denoted by the binding of splicing factors. These spliceosomes then
bend and pinch off portions of RNA, producing the final mRNA ready for
translation (Black, 2003). Splicing, therefore, serves two essential purposes –
to extricate noncoding intron segments and to combine multiple configurations of
exons in order to produce different sequences of mRNAs. . .
. . . Another major factor of splicing regulation involves the structure
of the pre-mRNA itself. Researchers have found that the variable structure of
the pre-mRNA either prevents or promotes access to specific splicing sites.
Additionally, it can centralize splicing signals in order to encourage splicing
(Warf & Berglund, 2010). Folding and splicing do not occur at distinct and
separate intervals either; in fact, transcription occurs while the structure of
the pre-mRNA is determined and the protein regulators are recruited. . .
. . . Indeed, the ubiquity of alternative splicing has led to increased
interest in its relation to numerous diseases. Recent studies have shown that
abnormal mRNA splicing in cancerous cells may explain some of their aberrant
behavior. One specific example involves the production of the enzyme DNMT3B,
which catalyzes DNA methylation. Abnormal splice forms of DNMT3B with retained
introns and misplaced promoters lead to atypical methylation patterns, which
cause the uncontrollable cell growth characteristic of tumorous cells
(Fackenthal & Godley, 2008).