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Figure 1. Classification of lncRNAs according to their genomic organization. Black box indicates exon; white box indicates intron; shade box indicates lncRNA.

Figure 2. Action modes of lncRNA. (A) lncRNAs such as Kcnq1ot1 and Xist recruit repressive chromatin modifying complex to suppress the expression of protein‐coding genes, thereby regulating imprinting; (B) enhancer RNAs (eRNAs) can initiate the process of transcription by binding to enhancer regions of DNA; (C) lncRNAs such as MALAT1 regulate alternative splicing (AS) of pre‐mRNA by modulating the level of active serine/arginine(SR) protein; (D) circular or linear lncRNAs can act as competing endogenous RNAs (ceRNAs) by binding to miRNAs; (E) some lncRNAs such as LINC00948, LINC00961 can encode micropeptides.

Teaching Material

Y. Kong, Z. Lu, P. Liu, Y. Liu, F. Wang, E. Y. Liang, F. F. Hou, M. Liang. Long Noncoding RNA: Genomics and Relevance to Physiology. Compr Physiol 9: 2019, 933-946.

Didactic Synopsis

Major Teaching Points:

• The mammalian cell expresses thousands of long non-coding RNAs (lncRNAs).
• lncRNAs can change the expression of protein-coding genes through transcriptional and posttranscriptional regulatory mechanisms.
• Deep sequencing, coupled with analysis of sequence characteristics, is the primary method used to identify lncRNAs.
• Physiological roles of specific lncRNAs can be examined using genetic targeting or knockdown with modified oligonucleotides.
• lncRNAs have been reported to contribute to the regulation of physiological functions and disease development in several organ systems, including cardiac hypertrophy, myocardial infarction, angiogenesis, endothelial function, hypertension and other aspects of the cardiovascular system, the kidney, skeletal muscles, the endocrine system, the digestive system, the respiratory system, the nervous system, and the reproductive system.
• The physiological role of the majority of lncRNAs, many of which are species- and tissue-specific, remains to be determined.

Didactic Legends

The figures—in a freely downloadable PowerPoint format—can be found on the Images tab along with the formal legends published in the article. The following legends to the same figures are written to be useful for teaching.

Figure 1 Teaching Points: lncRNAs can be classified based on their relations with nearby protein-coding genes. Sense lncRNAs are those that overlap a protein-coding gene on the sense strand. Antisense lncRNAs are located in antisense orientation to a protein-coding gene. Intronic lncRNAs are located in an intron of a protein-coding gene. Intergenic lncRNAs, also known as long intergenic noncoding RNAs (lincRNAs), are located between two protein-coding genes. Bidirectional lncRNAs are transcribed within 1000 base pairs away from promoters antisense to the protein-coding gene.

Figure 2 Teaching Points: lncRNAs play regulatory roles in gene expression at both the transcriptional and post-transcriptional levels. lncRNA transcripts can influence chromatin modification, imprinting, enhancer activities, pre-mRNA splicing, and mRNA translation, stability, and decay. lncRNAs also can sponge or compete with miRNAs. Some transcripts classified as lncRNAs may encode biologically functional peptides.