Abstract

BackgroundIntramuscular fat (IMF) is associated with meat quality and insulin resistance in animals. Research on genetic mechanism of IMF decomposition has positive meaning to pork quality and diseases such as obesity and type 2 diabetes treatment. In this study, an IMF trait segregation population was used to perform RNA sequencing and to analyze the joint or independent effects of genes and long intergenic non-coding RNAs (lincRNAs) on IMF.ResultsA total of 26 genes including six lincRNA genes show significantly different expression between high- and low-IMF pigs. Interesting, one lincRNA gene, named IMF related lincRNA (IRLnc) not only has a 292-bp conserved region in 100 vertebrates but also has conserved up and down stream genes (< 10 kb) in pig and humans. Real-time quantitative polymerase chain reaction (RT-qPCR) validation study indicated that nuclear receptor subfamily 4 group A member 3 (NR4A3) which located at the downstream of IRLnc has similar expression pattern with IRLnc. RNAi-mediated loss of function screens identified that IRLnc silencing could inhibit both of the RNA and protein expression of NR4A3. And the in-situ hybridization co-expression experiment indicates that IRLnc may directly binding to NR4A3. As the NR4A3 could regulate the catecholamine catabolism, which could affect insulin sensitivity, we inferred that IRLnc influence IMF decomposition by regulating the expression of NR4A3.ConclusionsIn conclusion, a novel functional noncoding variation named IRLnc has been found contribute to IMF by regulating the expression of NR4A3. These findings suggest novel mechanistic approach for treatment of insulin resistance in human beings and meat quality improvement in animal.

Highlights

  • Intramuscular fat (IMF) is associated with meat quality and insulin resistance in animals

  • The results showed that cells transfected with si-727 and si-2942 had significantly different IMF related lincRNA (IRLnc) expression levels than cells transfected with the negative control (NC) siRNA (Fig. 6a, P < 0.05), which indicates good knockdown efficiency

  • We found that the 292-bp conserved sequence of IRLnc had a very low energy requirement to interact with the 3′UTR region of NR4A3 mRNA

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Summary

Introduction

Intramuscular fat (IMF) is associated with meat quality and insulin resistance in animals. Research on genetic mechanism of IMF decomposition has positive meaning to pork quality and diseases such as obesity and type 2 diabetes treatment. Intramuscular fat (IMF) refers to the amount of fat located in skeletal muscle fibers [1]. Excess accumulation of IMF has been reported to be associated with diseases, such as type 2 diabetes and insulin resistance in humans [2]. As an important determinant of meat quality, IMF content directly influences flavor and juiciness and indirectly influences tenderness and meat color [1]. A total of 709 QTLs have been reported to be associated with pig IMF content (PigQTLdb, http://www.animalgenome.org/cgi-bin/QTLdb/SS/index, released at April 26, 2020) [6].

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