Progerin, an aberrant spliced form of Lamin A, is a potential therapeutic target for HGPS

Description

Alternative splicing is a biological operation that enables a messenger RNA to encode protein variants (isoforms) that give one gene several functions or properties. This process provides one of the major sources of use for understanding the proteomic diversity of multicellular organisms. In combination with post-translational modifications, it contributes to generating a variety of protein–protein interactions (PPIs) that are essential to cellular homeostasis or proteostasis. However, cells exposed to many kinds of stresses (aging, genetic changes, carcinogens, etc.) some-times derive cancer or disease onset from aberrant PPIs caused by DNA mutations, implying the PPIs from splicing variants may contribute to form a neomorphic protein complex, which has a gain (or loss) of function compared to the original protein complex. Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic disorder caused by the mutant protein, called as progerin.