Identification of chimeric RNAs in human infant brains and their implications in neural differentiation

Yue Tang; Shanshan Ma; Xinxin Wang; Qu Xing; Tuanjie Huang; Hongtao Liu; Qinghua Li; Yanting Zhang; Kun Zhang; Minghao Yao; Greta Luyuan Yang; Hui Li; Xingxing Zang; Bo Yang; Fangxia Guan

doi:10.1016/j.biocel.2019.03.012

Identification of chimeric RNAs in human infant brains and their implications in neural differentiation

Int J Biochem Cell Biol. 2019 Jun:111:19-26. doi: 10.1016/j.biocel.2019.03.012. Epub 2019 Apr 5.

Authors

Yue Tang¹, Shanshan Ma², Xinxin Wang³, Qu Xing², Tuanjie Huang², Hongtao Liu², Qinghua Li², Yanting Zhang², Kun Zhang², Minghao Yao², Greta Luyuan Yang⁴, Hui Li⁵, Xingxing Zang⁶, Bo Yang⁷, Fangxia Guan⁸

Affiliations

¹ School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China; School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China; Henan Provincial People's Hospital, Zhengzhou, 450003, Henan, China.
² School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China.
³ Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
⁴ Stuyvesant High School, NY, USA.
⁵ School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China; Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA, USA.
⁶ Einstein College of Medicine, Department of Microbiology and Immunology, 1300 Morris Park Ave, Bronx, NY, 10461, USA.
⁷ Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
⁸ School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China; Henan Provincial People's Hospital, Zhengzhou, 450003, Henan, China; The Translational Medical Center of First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. Electronic address: [email protected].

PMID: 30959201
DOI: 10.1016/j.biocel.2019.03.012

Abstract

Chimeric RNAs are transcripts composed of RNA fragments from different genes and are traditionally well-known cancer-causing genetic events. Recent studies show chimeric RNAs being present in multiple non-neoplastic tissues and cells, suggesting that at least some may have roles in normal physiology. However, chimeric RNAs and their implications in brain development and neural differentiation have not been formally studied. Here, we firstly characterized the landscape of chimeric RNAs in human infant brain tissues and identified 599 chimeric RNAs. Through a series of filtering, 22 were selected and tested in a neural differentiation process starting from stem cells. Ten were validated experimentally. One of these ten chimeric RNAs, DUS4L-BCAP29, dramatically increased when human umbilical mesenchymal stem cells were induced for neural differentiation. Consistently, we found that overexpressed DUS4L-BCAP29 effectively promoted neural differentiation. Our results support the important role(s) chimeric RNAs play in neural differentiation, and are consistent with the new notion that chimeric RNAs also exist in normal physiology, and likely serve biological purposes.

Keywords: Brain; Chimeric RNAs; DUS4L-BCAP29; Mesenchymal stem cells; Neural differentiation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Brain / cytology*
Cell Differentiation / genetics*
Gene Fusion / genetics
Humans
Infant
Membrane Proteins / genetics
RNA, Messenger / genetics

Substances

BCAP29 protein, human
Membrane Proteins
RNA, Messenger