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ZFIN ID: ZDB-PUB-170526-6
Ectopically expressed Slc34a2a sense-antisense transcripts cause a cerebellar phenotype in zebrafish embryos depending on RNA complementarity and Dicer
Piatek, M.J., Henderson, V., Fearn, A., Chaudhry, B., Werner, A.
Date: 2017
Source: PLoS One   12: e0178219 (Journal)
Registered Authors:
Keywords: none
MeSH Terms:
  • Animals
  • Cerebellum/growth & development
  • Cerebellum/metabolism
  • DEAD-box RNA Helicases/antagonists & inhibitors
  • DEAD-box RNA Helicases/genetics*
  • DEAD-box RNA Helicases/metabolism
  • Embryo, Nonmammalian/metabolism
  • Embryonic Development/genetics
  • Gene Expression Regulation, Developmental
  • In Situ Hybridization
  • Morpholinos/metabolism
  • RNA Interference
  • RNA, Complementary/metabolism*
  • RNA, Small Interfering/metabolism
  • Sodium-Phosphate Cotransporter Proteins, Type IIb/antagonists & inhibitors
  • Sodium-Phosphate Cotransporter Proteins, Type IIb/genetics*
  • Sodium-Phosphate Cotransporter Proteins, Type IIb/metabolism
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 28542524 Full text @ PLoS One
Natural antisense transcripts (NATs) are complementary to protein coding genes and potentially regulate their expression. Despite widespread occurrence of NATs in the genomes of higher eukaryotes, their biological role and mechanism of action is poorly understood. Zebrafish embryos offer a unique model system to study sense-antisense transcript interplay at whole organism level. Here, we investigate putative antisense transcript-mediated mechanisms by ectopically co-expressing the complementary transcripts during early zebrafish development. In zebrafish the gene Slc34a2a (Na-phosphate transporter) is bi-directionally transcribed, the NAT predominantly during early development up to 48 hours after fertilization. Declining levels of the NAT, Slc34a2a(as), coincide with an increase of the sense transcript. At that time, sense and antisense transcripts co-localize in the endoderm at near equal amounts. Ectopic expression of the sense transcript during embryogenesis leads to specific failure to develop a cerebellum. The defect is RNA-mediated and dependent on sense-antisense complementarity. Overexpression of a Slc34a2a paralogue (Slc34a2b) or the NAT itself had no phenotypic consequences. Knockdown of Dicer rescued the brain defect suggesting that RNA interference is required to mediate the phenotype. Our results corroborate previous reports of Slc34a2a-related endo-siRNAs in two days old zebrafish embryos and emphasize the importance of coordinated expression of sense-antisense transcripts. Our findings suggest that RNAi is involved in gene regulation by certain natural antisense RNAs.