title: Intronic cleavage and polyadenylation regulates gene expression during DNA damage response through U1 snRNA.
abstract: The DNA damage response involves coordinated control of gene expression and DNA repair. Using deep sequencing, we found widespread changes of alternative cleavage and polyadenylation site usage on ultraviolet-treatment in mammalian cells. Alternative cleavage and polyadenylation regulation in the 3' untranslated region is substantial, leading to both shortening and lengthening of 3' untranslated regions of genes. Interestingly, a strong activation of intronic alternative cleavage and polyadenylation sites is detected, resulting in widespread expression of truncated transcripts. Intronic alternative cleavage and polyadenylation events are biased to the 5' end of genes and affect gene groups with important functions in DNA damage response and cancer. Moreover, intronic alternative cleavage and polyadenylation site activation during DNA damage response correlates with a decrease in U1 snRNA levels, and is reversible by U1 snRNA overexpression. Importantly, U1 snRNA overexpression mitigates ultraviolet-induced apoptosis. Together, these data reveal a significant gene regulatory scheme in DNA damage response where U1 snRNA impacts gene expression via the U1-alternative cleavage and polyadenylation axis.
authors.affiliation: Chemistry Department, Belfer Research Building, Hunter College and Graduate Center, City University of New York , New York, NY, USA.
authors.forename: Emral
authors.initials: E
authors.lastname: Devany
authors.affiliation: Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School , Newark, NJ, USA.
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Park
authors.affiliation: Chemistry Department, Belfer Research Building, Hunter College and Graduate Center, City University of New York , New York, NY, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Murphy
authors.affiliation: Chemistry Department, Belfer Research Building, Hunter College and Graduate Center, City University of New York , New York, NY, USA.
authors.forename: George
authors.initials: G
authors.lastname: Zakusilo
authors.affiliation: Chemistry Department, Belfer Research Building, Hunter College and Graduate Center, City University of New York , New York, NY, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Baquero
authors.affiliation: Chemistry Department, Belfer Research Building, Hunter College and Graduate Center, City University of New York , New York, NY, USA.
authors.forename: Xiaokan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School , Newark, NJ, USA.
authors.forename: Mainul
authors.initials: M
authors.lastname: Hoque
authors.affiliation: Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School , Newark, NJ, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Tian
authors.affiliation: Chemistry Department, Belfer Research Building, Hunter College and Graduate Center, City University of New York , New York, NY, USA.
authors.forename: Frida E
authors.initials: FE
authors.lastname: Kleiman
keywords: DNA damage response; U1 snRNP; alternative polyadenylation