Evidence that cleavage factor Im is a heterotetrameric protein complex controlling alternative polyadenylation

摘要: Recent estimates indicate that ∼60% of human genes include alternative polyadenylation sites. Hence, control can have a great impact on gene expression and cellular function. Cleavage factor (CF) Im is 3′-end processing essential for in vitro processing. CFIm purified from HeLa cells associated with three polypeptides 25, 59 68 kD, it generally thought to be heterodimer composed the 25-kD subunit one larger subunits. Previously, we serendipitously discovered knockdown CFIm25 causes an upstream shift utilization Here, investigated whether this because inherent property complex and, if so, what structural elements are important its The major conclusions study (i) contrary previous assumptions, forms stable heterotetramers through dimerization (ii) per se responsible polyadenylation. (iii) However, structurally related CFIm68 CFIm59 functionally redundant (iv) appears higher specific activity. Thus, establishes not only plays general role but also regulatory poly(A) site selection.