Mechanism of STMN2 cryptic splice-polyadenylation and its correction for TDP-43 proteinopathies

• DOI: 10.1126/science.abq5622
• Publication Date: 2023-03-16T17:58:26Z
• Authors: Michael W. Baughn; Ze’ev Melamed; Jone López-Erauskin; Melinda S. Beccari; Karen Ling; Aamir Zuberi; Maximilliano Presa; Elena Gonzalo-Gil; Roy Maimon; Sonia Vazquez-San...; Som Chaturvedi; Mariana Bravo-Her...; Vanessa Taupin; Stephen Moore; Jonathan W. Artates; Eitan Acks; I. Sandra Ndayambaje; Ana R. Agra de Al...; Paayman Jafar-nejad; Frank Rigo; C. Frank Bennett; Cathleen Lutz; Clotilde Lagier-T...; Don W. Cleveland
• Keywords: Stathmin

Loss of nuclear TDP-43 is a hallmark neurodegeneration in proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). mislocalization results cryptic splicing polyadenylation pre-messenger RNAs (pre-mRNAs) encoding stathmin-2 (also known as SCG10), protein that required for axonal regeneration. We found binding to GU-rich region sterically blocked recognition the 3' splice site