Predominance of spliceosomal complex formation over polyadenylation site selection in TDP-43 autoregulation.

ABSTRACT: TDP-43 is a nuclear protein involved in many aspects of RNA metabolism. To ensure cellular viability, its expression levels within cells must be tightly regulated. We have previously demonstrated that TDP-43 autoregulation occurs through the activation of a normally silent intron in its 3'-UTR sequence that results in the use of alternative polyadenylation sites. In this work, we analyse which is the dominant event in autoregulation: the recognition of the splice sites of 3'-UTR intron 7 or the intrinsic quality of the alternative polyadenylation sites. A panel of minigene constructs was tested for autoregulation functionality, protein production and subcellular messenger RNA localization. Our data clearly indicate that constitutive spliceosome complex formation across intron 7 does not le

SUBMITTER: Bembich S 

PROVIDER: S-EPMC3950720 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature