The mammalian cell expresses thousands of long noncoding RNAs (lncRNAs) that are longer than 200 nucleotides but do not encode any protein. lncRNAs can change the expression of protein-coding genes through both cis and trans mechanisms, including imprinting and other types of transcriptional regulation, and posttranscriptional regulation including serving as molecular sponges. 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. Identification of nucleic acids or proteins with which an lncRNA interacts is essential for understanding the molecular mechanism underlying its physiological role. lncRNAs have been reported to contribute to the regulation of physiological functions and disease development in several organ systems, including the cardiovascular, renal, muscular, endocrine, digestive, nervous, respiratory, and reproductive systems. The physiological role of the majority of lncRNAs, many of which are species and tissue specific, remains to be determined. © 2019 American Physiological Society. Compr Physiol 9:933-946, 2019.
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