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Long non-coding RNAs in regulation of adipogenesis and adipose tissue function

  1. Tiziana Squillaro
  2. Gianfranco Peluso
  3. Umberto Galderisi
  4. Giovanni Di Bernardo  Is a corresponding author
  1. Department of Experimental Medicine, Biotechnology, and Molecular Biology Section, University of Campania Luigi Vanvitelli, Italy
  2. Institute Bioscience and BioResources, CNR, Italy
Review Article
Cite this article as: eLife 2020;9:e59053 doi: 10.7554/eLife.59053
3 figures and 1 table

Figures

Types of RNAs present in eukaryotic cells.

RNAs are primarily divided between coding RNAs and noncoding RNAs. Coding RNAs contain one class of molecules: the messenger RNAs (mRNAs) that undergo the translation process. The other category contains noncoding RNAs, since they are not translated into proteins. Ribosomal RNAs (rRNAs) and transfer RNAs (tRNAs) are the two most abundant classes of noncoding RNAs, but several other RNA types have specific roles in eukaryotic cells. These other RNAs are usually divided into two groups: short noncoding RNAs (sncRNAs), consisting of RNAs with a length of less than 200 nucleotides; and long noncoding RNAs (lncRNAs). The exact percentages of the various ncRNA classes are still under debate and the indicated values are reported in many studies.

Some examples of lncRNA activity as a regulator of gene expression.

LncRNAs, working on proximal loci or at a great distance, can inhibit or activate the expression gene at various levels: i) chromatin modification and remodeling; ii) transcriptional control, and iii) post-transcriptional control. Panel A summarizes the different chromatin remodeling mechanisms. From left to right: nucleotide covalent modifiers (methylation) at CpG island (TET, DNMT enzymes); histone covalent modifiers, which regulate amino acid methylation (LSD, SET1 enzymes) and acetylation (HADC and HAT enzymes); ATP-dependent chromatin remodeling complexes (SWI/SNF, NURD, CHRAC). The lncRNAs acting with different enzymatic complexes are depicted with red squares. Panel B shows lncRNAs involved in the early transcription stages. LncRNAs acquiring a specific R-loops structure interact with PIC (Preinitiation Complex) to modulate transcription by recruiting regulator factors. The lncRNA acting with different transcription regulators is depicted with a red square. Panel C shows some post-transcription activities of lncRNAs. Top: MALAT1 localizes to interchromatin granule clusters (nuclear speckles) and regulates alternative splicing by modulating the distribution and the levels of active SR splicing factors. Bottom: ZEB2/SIP1 NAT binds and masks specific splicing sites, causing intron retention. The retained intron contains an IRES site (internal ribosome entry site) that induces a more efficient ZEB2 protein translation. The lncRNAs acting with different enzymatic complexes are depicted with red squares.

Summary of lncRNAs activity during adipogenesis.

Mesenchymal stromal cells contain stem cells that can be committed to white or brown precursor cells able to differentiate in white or brown adipocytes, respectively. A specific subpopulation of white adipocytes can transdifferentiate in brite/beige adipocytes following thermogenic stimuli. The picture shows several lncRNAs involved in adipocyte maturation and/or in brite/beige transdifferentiation. For each lncRNA is indicated the molecular mechanism of action: regulation of transcription or post-transcription or translation. The lncRNAs that can be target of antisense oligonucleotide (ASO) therapy are depicted.

Tables

Table 1
Size and accession number of cited lncRNAs involved in adipogenesis.
Homo sapiensMus musculus
Blnc1759 nt URS0000DBDC4C_9606965 nt URS0000D77FA2_10090
Lnc-BATE1894 nt URS000075C5E3_10090
AK079912N.D.N.D.
LncBATE101808 nt URS000075F077_10090
MIAT10,194 nt URS00007E4AF8_96069163 nt URS0000760956_10090
LINC01119*1210 nt URS000075CEA4_9606
LINC02202 *2863 nt URS000075A437_9606
NONMMUG024827N.DN.D.
H19*2.362 nt URS0000812128_9602286 nt URS0000767B73_10090
ASMER-1N.D.N.D.
ASMER-2N.D.N.D.
Plnc1N.D.N.D.
SRA875 nt URS00001A8152_9606829 nt URS00003EA2D2_10090
ADINR2252 nt URS0000CCE086_9606
HOTAIR*2364 nt URS000075C808_96062222 nt URS000075BAE8_10090
PVT1*1957 nt URS00008E3A67_96063319 nt URS000077AEFF_10090
  1. *These lncRNAs have alternative transcripts.

    N.D. Not Detected in RNA database (https://rnacentral.org).

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