Lamin A / Progerin

Lamin A is a type-V intermediate filament protein and major structural component of the nuclear lamina — the meshwork underlying the inner nuclear membrane — that is essential for nuclear shape, chromatin organisation, DNA repair and gene regulation. It is encoded by LMNA and undergoes post-translational farnesylation and processing before its precursor, prelamin A, is cleaved by the endoprotease ZMPSTE24 to yield mature lamin A. Progerin is a truncated, permanently farnesylated isoform produced by a cryptic splice-site mutation in LMNA that causes the premature ageing syndrome Hutchinson-Gilford progeria; progerin accumulates at low levels during normal ageing and disrupts nuclear architecture, the DNA-damage response and heterochromatin, making it a model for studying molecular mechanisms of physiological ageing at the nuclear envelope.