The number of human LncRNAs has now exceeded all known protein-coding genes. Most studies of human LncRNAs have been conducted in cell culture systems where various mechanisms of action have been worked out. On the other hand, efforts to elucidate the function of human LncRNAs in an in vivo setting have been limited. In this brief review, we highlight some strengths and weaknesses of studying human LncRNAs in the mouse. Special consideration is given to bacterial artificial chromosome transgenesis and genome editing. The integration of these technical innovations offers an unprecedented opportunity to complement and extend the expansive literature of cell culture models for the study of human LncRNAs. Two different examples of how BAC transgenesis and genome editing can be leveraged to gain insight into human LncRNA regulation and function in mice are presented: the random integration of a vascular cell-enriched LncRNA and a targeted approach for a new LncRNA immediately upstream of the ACE2 gene, which encodes the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent underlying the coronavirus disease-19 (COVID-19) pandemic. 

https://link.springer.com/content/pdf/10.1007/s00335-022-09943-2.pdf

Of mice and human-specific long noncoding RNAs

Simple Summary The kidding number is an important reproductive trait in domestic goats. The oviduct, as one of the most major organs, is directly involved in the reproductive process, providing nutrition and a location for early embryonic development. The current study provides genome-wide expression profiles of mRNA and long noncoding RNAs (lncRNAs) expression in Yunshang black goat, a new breed of meat goat bred in China with a high kidding number. During the luteal phases, oviduct mRNAs and lncRNAs associated with high- and low-fecundity Yunshang black goats were identified, and their potential biological functions were predicted using GO, KEGG, and GSEA enrichment analysis. These findings shed light on the oviduct-based prolificacy mechanism in goats. Abstract The oviduct is associated with embryo development and transportation and regulates the pregnancy success of mammals. Previous studies have indicated a molecular mechanism of lncRNAs in gene regulation and reproduction. However, little is known about the function of lncRNAs in the oviduct in modulating goat kidding numbers. Therefore, we combined RNA sequencing (RNA-seq) to map the expression profiles of the oviduct at the luteal phase from high- and low-fecundity goats. The results showed that 2023 differentially expressed mRNAs (DEGs) and 377 differentially expressed lncRNAs (DELs) transcripts were screened, and 2109 regulated lncRNA-mRNA pairs were identified. Subsequently, the genes related to reproduction (IGF1, FGFRL1, and CREB1) and those associated with embryonic development and maturation (DHX34, LHX6) were identified. KEGG analysis of the DEGs revealed that the GnRH- and prolactin-signaling pathways, progesterone-mediated oocyte maturation, and oocyte meiosis were related to reproduction. GSEA and KEGG analyses of the target genes of DELs demonstrated that several biological processes and pathways might interact with oviduct functions and the prolificacy of goats. Furthermore, the co-expression network analysis showed that XLOC_029185, XLOC_040647, and XLOC_090025 were the cis-regulatory elements of the DEGs MUC1, PPP1R9A, and ALDOB, respectively; these factors might be associated with the success of pregnancy and glucolipid metabolism. In addition, the GATA4, LAMA2, SLC39A5, and S100G were trans-regulated by lncRNAs, predominantly mediating oviductal transport to the embryo and energy metabolism. Our findings could pave the way for a better understanding of the roles of mRNAs and lncRNAs in fecundity-related oviduct function in goats.

/pdf/oviduct-transcriptomic-reveals-the-regulation-of-mrnas-and-3e75nyuo.pdf

Oviduct Transcriptomic Reveals the Regulation of mRNAs and lncRNAs Related to Goat Prolificacy in the Luteal Phase

LncRNA THOR promotes endometrial cancer progression through the AKT and ERK signaling pathways

Long non-coding RNAs (lncRNAs) are a class of transcriptional RNA molecules, which play critical roles in diverse biological processes. However, little is known about the overall expression pattern and roles of lncRNAs in skeletal muscle of largemouth bass (LMB). Here, we constructed two skeletal muscle RNA libraries to find lncRNAs that may involve in the regulation of skeletal muscle development between juvenile and adult LMB. A total of 16,147 lncRNAs and 4611 differentially expressed lncRNAs were identified. Among these identified lncRNAs, 10 lncRNAs were randomly selected to confirm their expression by real-time qPCR both in libraries, which were consistent with the RNA sequencing results. The target mRNAs of lncRNAs were predicted for GO enrichment analysis. Results showed that these targets associated with growth and development of muscle, such as skeletal muscle fiber development, myoblast proliferation and differentiation. Importantly, correlation analysis of lncRNA-miRNA-mRNA regulatory network revealed that several lncRNAs targeted miRNAs which are closely involved in the regulation of muscle development. It is the first time to identify a number of lncRNA that correlate with skeletal muscle development in LMB. Our results not only provide a comprehensive expression profile of muscle lncRNAs in this species, but also provide a theoretical basis for further elaborating genetic regulation mechanism of muscle growth and development, and pave the way for the future molecular assisted breeding in carnivorous fishes. 

Identification and characterization of long non-coding RNAs in juvenile and adult skeletal muscle of largemouth bass (Micropterus salmoides).

THOR is a highly conserved testis-specific long noncoding RNA (lncRNA). The interaction between THOR and the development of the male reproductive system remains unclear. Herein, CRISPR/Cas9 technology was used to establish a stable THOR-deficient mouse model, and the relationship between THOR and the fertility of adult male mice was investigated. The male mice in which THOR was deleted were smaller than the WT male mice. Moreover, their survival rate was reduced by 60%, their fertility was reduced by 50%, their testicular size and sperm motility were reduced by 50%, their testicular cell apoptosis was increased by 7-fold, and their ratio of female-to-male offspring was imbalanced (approximately 1:3). Furthermore, to elucidate the mechanisms of male reproductive system development, the mRNA levels of THOR targets were measured by qRT-PCR. Compared with WT mice, the THOR-deficient mice exhibited significantly decreased mRNA levels of IGF2BP1, c-MYC, IGF1, and IGF2. MEK-ERK signaling pathway expression was downregulated as determined by Western blot. We found that THOR targeted the MER-ERK signaling pathway downstream of IGF2 by binding to IGF2BP1 and affected testicular and sperm development in male mice. These results may also provide perspectives for exploring the roles of lncRNAs in human reproductive development and the pathogenesis and potential therapeutic targets of infertility.

https://www.mdpi.com/2227-9059/9/8/859/pdf

Lin Zhou

Papers

Investigation of the lncRNA THOR in Mice Highlights the Importance of Noncoding RNAs in Mammalian Male Reproduction.