A long noncoding RNA cluster-based genomic locus maintains proper development and visual function

Author:

Wang Fei1,Ren Dalong1,Liang Xiaolin1,Ke Shengwei1,Zhang Bowen1,Hu Bing1,Song Xiaoyuan1,Wang Xiangting1ORCID

Affiliation:

1. Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, China

Abstract

Abstract Long noncoding RNAs (lncRNAs) represent a group of regulatory RNAs that play critical roles in numerous cellular events, but their functional importance in development remains largely unexplored. Here, we discovered a series of previously unidentified gene clusters harboring conserved lncRNAs at the nonimprinting regions in brain (CNIBs). Among the seven identified CNIBs, human CNIB1 locus is located at Chr 9q33.3 and conserved from Danio rerio to Homo sapiens. Chr 9q33.3-9q34.11 microdeletion has previously been linked to human nail-patella syndrome (NPS) which is frequently accompanied by developmental and visual deficiencies. By generating CNIB1 deletion alleles in zebrafish, we demonstrated the requirement of CNIB1 for proper growth and development, and visual activities. Furthermore, we found that the role of CNIB1 on visual activity is mediated through a regulator of ocular development-lmx1bb. Collectively, our study shows that CNIB1 lncRNAs are important for zebrafish development and provides an lncRNA cluster-mediated pathophysiological mechanism for human Chr 9q33.3-9q34.11 microdeletion syndrome.

Funder

National Natural Science Foundation of China

Fundamental Research Funds for the Central Universities

Development Foundation of Hefei Center for Physical Science and Technology

Publisher

Oxford University Press (OUP)

Subject

Genetics

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