Search Results for: endogenous sponge

Endogenous miRNA Sponge lincRNA-RoR Regulates Oct4, Nanog, and Sox2 in Human Embryonic Stem Cell Self-Renewal

lncRNA

The embryonic stem cell (ESC) transcriptional and epigenetic networks are controlled by a multilayer regulatory circuitry, including core transcription factors (TFs), posttranscriptional modifier microRNAs (miRNAs), and some other regulators. However, the role of large intergenic noncoding RNAs (lincRNAs) in this regulatory circuitry and their underlying mechanism remains undefined.

Here, researchers from the Second Military Medical University, China demonstrate that a lincRNA, linc-RoR, may function as a key competing endogenous RNA to link the network of miRNAs and core TFs, e.g., Oct4, Sox2, and Nanog. They show that linc-RoR shares miRNA-response elements with these core TFs and that linc-RoR prevents these core TFs from miRNA-mediated suppression in self-renewing human ESC. They suggest that linc-RoR forms a feedback loop with core TFs and miRNAs to regulate ESC maintenance and differentiation. These results may provide insights into the functional interactions of the components of genetic networks during development and may lead to new therapies for many diseases.

lncRNA

  • Wang Y, Xu Z, Jiang J, Xu C, Kang J, Xiao L, Wu M, Xiong J, Guo X, Liu H. (2013) Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal. Dev Cell 25(1), 69-80. [abstract]

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  • endogenous sponge

Non-Coding RNA and Evolution of Complexity

lncRNA

Non-coding DNA in genomes increases in concert with the increase in developmental complexity in evolution, and is consonant with the important regulatory roles identified for the many classes of non-coding RNAs transcribed from more than 85 % of the DNA regarded as ‘junk’ not so long ago Dr Mae-Wan Ho

A vast RNA underworld exposed

It wasn’t so long ago that most people still believed DNA carries the instructions for making an organism, while RNA simply copies out (transcribes) the instructions (by complementary base pairing) that are then translated into protein via a genetic code, in which different triplets of bases (codons) specify one of twenty amino acids plus start and stop signals. The proteins are the real workhorses in this hierarchy, with the DNA akin to the Holy Scripture – ‘Book of Life’ the Central Dogma – faithfully copied and transmitted by scribes (RNA), to be interpreted and implemented by the faithful (proteins).

But soon after the human genome sequence was announced, it became clear that RNA plays a much more substantive, central role than previously thought.

Incoming search terms:

  • are all lncRNA spliced
  • how many protiens are coded by human dna

Long Noncoding RNA: “LNCs” to Cancer

lncRNA

In recent years we have witnessed a paradigm shift concerning the long-lasting controversy over “junk DNA” in the human genome. It is now well established that, besides the roughly 25 000 protein-coding genes, the genome contains tens of thousands of functional elements. In addition, the completion of the ENCODE project—the functional annotation of all regulatory regions of the human genome—has confirmed that 80% of genome is transcribed into RNA, whereas <than 2% is translated into proteins. Thus, an as yet unknown number of transcripts lacking significant coding potential, including long noncoding RNAs (lncRNAs), exceed the number of protein-coding genes . However, the expression, regulation, sequence, function, and mechanism of action of the vast majority of lncRNAs are currently largely unknown.

The Intertwining of Transposable Elements and Non-Coding RNAs

lncRNA

Growing evidence shows a close association of transposable elements (TE) with non-coding RNAs (ncRNA), and a significant number of small ncRNAs originate from TEs. Further, ncRNAs linked with TE sequences participate in a wide-range of regulatory functions. Alu elements in particular are critical players in gene regulation and molecular pathways. Alu sequences embedded in both long non-coding RNAs (lncRNA) and mRNAs form the basis of targeted mRNA decay via short imperfect base-pairing. Imperfect pairing is prominent in most ncRNA/target RNA interactions and found throughout all biological kingdoms. The piRNA-Piwi complex is multifunctional, but plays a major role in protection against invasion by transposons. This is an RNA-based genetic immune system similar to the one found in prokaryotes, the CRISPR system. Thousands of long intergenic non-coding RNAs (lincRNAs) are associated with endogenous retrovirus LTR transposable elements in human cells. These TEs can provide regulatory signals for lincRNA genes. A surprisingly large number of long circular ncRNAs have been discovered in human fibroblasts. These serve as “sponges” for miRNAs. Alu sequences, encoded in introns that flank exons are proposed to participate in RNA circularization via Alu/Alu base-pairing. Diseases are increasingly found to have a TE/ncRNA etiology. A single point mutation in a SINE/Alu sequence in a human long non-coding RNA leads to brainstem atrophy and death. On the other hand, genomic clusters of repeat sequences as well as lncRNAs function in epigenetic regulation. Some clusters are unstable, which can lead to formation of diseases such as facioscapulohumeral muscular dystrophy. The future may hold more surprises regarding diseases associated with ncRNAs andTEs.

  • Hadjiargyrou M, Delihas N. (2013) The Intertwining of Transposable Elements and Non-Coding RNAs. Int J Mol Sci 14(7), 13307-28. [article]