Reverse-genetics studies of lncRNAs—what we have learnt and paths forward

Abstract

Long non-coding RNAs (lncRNAs) represent a major fraction of the transcriptome in multicellular organisms. Although a handful of well-studied lncRNAs are broadly recognized as biologically meaningful, the fraction of such transcripts out of the entire collection of lncRNAs remains a subject of vigorous debate. Here we review the evidence for and against biological functionalities of lncRNAs and attempt to arrive at potential modes of lncRNA functionality that would reconcile the contradictory conclusions. Finally, we discuss different strategies of phenotypic analyses that could be used to investigate such modes of lncRNA functionality.

Trans- and cis-acting effects of Firre on epigenetic features of the inactive X chromosome

“…WT Log(Firre -/-/WT) tissue-specific, as proposed for other lncRNAs 50 . Consistent with the role of Firre in hematopoiesis, local changes were observed in CLPs and CD8 + T cells around the Firre locus, revealing a celltype-specific role in cis-maintenance of H3K27me3 33 .…”

“…For example, mice homozygous for deletions of regions harboring 1243 noncoding sequences had no distinguishable phenotypes 87 . Similarly, mice with deletions of nine conserved lncRNAs including Malat were viable with no obvious abnormalities 50,88 . Firre KO mice have few abnormal phenotypes except for abnormalities in B-and T-cell physiology 33 .…”

Systematic and computational identification of Androctonus crassicauda long non-coding RNAs

“…By the special role of lncRNAs in regulating gene expression, controlling various biological processes, and cellular functions 3 , 5 , 7 , their identification which leads to the discovery of many sophisticate mechanisms of gene regulation has become important in different species. Development of high-throughput sequencing cooperated with bioinformatics tools, has aid lncRNAs uncover in many insect species 4 , 12 , 13 .…”

“…Currently, due to lncRNAs functionality in regulating neighbor protein-coding genes expression, mRNAs stability, post-translational modifications, translation, epigenetic modifications, DNA methylation, and their ability to interact with diverse macro-molecules 3 , 5 , 7 , they attracted the attention of scientists. Despite the important role of lncRNAs in biological processes, a limited number of studies focus on non-model animal lncRNAs.…”

Identification of Biomarkers of Hepatocellular Carcinoma Gene Prognosis Based on Immune-Related lncRNA Signature of Transcriptome Data

“…In the past few years, long non-coding RNA (lncRNA) has attracted attention in tumor research. They are a class of non-coding RNAs (ncRNAs) longer than 200 nucleotides that have no protein-coding potential (Gao et al, 2020). At present, there are more than 20 lncRNAs being studied for human cancer and medical applications.…”