Regulation of Constitutive Tip110 Expression in Human Cord Blood CD34+ Cells Through Selective Usage of the Proximal and Distal Polyadenylation Sites Within the 3'Untranslated Region

Stem Cells Dev. 2018 Apr 15;27(8):566-576. doi: 10.1089/scd.2017.0197. Epub 2018 Mar 27.

Abstract

Tip110 plays important roles for stem cell pluripotency and hematopoiesis. However, little is known about the regulatory mechanisms of Tip110 expression in this process. In this study, we first showed that constitutive Tip110 expression was cell proliferation and differentiation dependent and self-regulated in both human cord blood CD34+ cells. Using a series of molecular techniques, we found that ectopic Tip110 expression led to increased constitutive Tip110 expression through its 3'-untranslated region (3'UTR), specifically through preferential usage of proximal polyadenylation sites within its 3'UTR in cells, including human cord blood CD34+ cells, which indeed led to an increased number of CD34+ cells during differentiation of those cells. Lastly, we showed that Tip110 protein interacted with cleavage stimulation factor 64 (CstF64) protein and that more CstF64 was recruited to the promixal polyadenylation site than the distal polyadenylation site within its 3'UTR. These finding together demonstrates that constitutive Tip110 expression is regulated, at least in part, through its interaction with CstF64, recruitment of CstF64 to, and selective usage of those two polyadenylation sites within its 3'UTR.

Keywords: 3′UTR; CD34+; Tip110; hematopoiesis; miRNA.

MeSH terms

  • 3' Untranslated Regions
  • Antigens, CD34 / genetics*
  • Antigens, CD34 / metabolism
  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / metabolism
  • Cell Differentiation
  • Cell Proliferation
  • Cleavage Stimulation Factor
  • Fetal Blood / cytology
  • Fetal Blood / metabolism*
  • Gene Expression Regulation
  • HEK293 Cells
  • Hematopoiesis / genetics*
  • Humans
  • K562 Cells
  • Polyadenylation
  • Primary Cell Culture
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism

Substances

  • 3' Untranslated Regions
  • Antigens, CD34
  • Antigens, Neoplasm
  • CSTF2T protein, human
  • Cleavage Stimulation Factor
  • RNA-Binding Proteins
  • SART3 protein, human