Genome-wide detection of RNA editing events during the hair follicles cycle of Tianzhu white yak

Abstract

Background: The hair coat is available for the yak to live in the harsh environment of the plateau. Besides, improving the hair production of yak is necessary for its textile industry development. Hair grows from hair follicles (HFs). The HFs undergo periodic growth after birth and are regulated by the complex gene regulatory network. However, the molecular mechanism of HFs regeneration in the Tianzhu white yak remains unclear. RNA editing is a post-transcriptional mechanism that regulates gene expression and produces new transcripts. Hence, we investigated the influence of the A-to-I RNA editing events on the HFs cycle of the Tianzhu white yak.

Results: We finally identified 54,707 adenosine-to-inosine (A-to-I) RNA editing sites (RESs) from RNA sequencing data of the HFs cycle in the Tianzhu white yak. Annotation results showed RESs caused missense amino acid changes in 7 known genes. And 202 A-to-I editing sites altered 23 target genes of 140 microRNAs. A total of 1,722 differential RESs were identified during the HFs cycle of Tianzhu white yak. GO and KEGG enrichment analysis revealed several signaling pathways and GO terms involved skin development, hair growth, and HFs cycle. Such as genes with differential RNA editing levels were significantly enriched in the peroxisome, metabolic pathways, Notch signaling pathway, and PPAR signaling pathway. Besides, the editing sites in HFs development-related genes FAS, APCDD1, WWOX, MPZL3, RUNX1, KANK2, DCN, DSC2, LEPR, HEPHL1, and PTK2B were suggested as the potential RESs involving HFs development.

Conclusion: This study investigated the global A-to-I RNA editing events during the HFs cycle of yak skin tissue and expanded the knowledge of A-to-I RNA editing on the HFs cycle. Furthermore, this study revealed that RNA editing-influenced genes may regulate the HFs cycle by participating in the HFs development-related pathways. The findings might provide new insight into the regulation of RNA editing in hair growth.

Keywords: Differential RNA editing sites; Hair follicles cycle; RNA editing; Tianzhu white yak.

Fig. 1

The overview of identified RNA editing events. (a, b) The statistical analysis of RNA editing types; (c) The number of the regular and hyper RNA editing sites; (d) The editing ratio distribution of all A-to-I editing events in different stages of the HFs cycle, editing level was calculated by the average editing level of three biological replicates of each stage; (e) Genomic distribution of RESs and the percentage of RESs caused missense variant in protein-coding region

Fig. 2

The influence of A-to-I editing events on miRNA binding genes and the sequence preference of A-to-I editing sites. (a) The Venn diagram of RNA editing altered miRNA binding sites, the intersection of UT represents loss target sites of miRNA; the intersection of ET represents the gain target sites of miRNA; (b) Top 10 pathways and top 10 GO terms of altered target genes of miRNAs; (c) Sequence preferences of the neighborhoods of hyper A-to-I editing sites; (d) Sequence preferences of the neighborhoods of regular A-to-I editing sites

Fig. 3

The differential RESs analysis and key RESs investigation. (a) PCA analysis of 15 skin samples; (b) Heatmap of the differential RESs; (c) Top 10 pathways and top 10 GO terms of the differential RESs edited genes (Jan vs. Mar); (d) Top 10 pathways and top 10 GO terms of the differential RESs edited genes (Jan vs. Oct); (e) Top 10 pathways and top 10 GO terms of the differential RESs edited genes (Mar vs. Oct); (f) The PPI network of all differential RESs between the different period of HFs cycle, the size indicates node degree