The development and controversy of competitive endogenous RNA hypothesis in non-coding genes
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The development and controversy of competitive endogenous RNA hypothesis in non‑coding genes Weimin Lin1 · Hongcheng Liu1 · Yonghang Tang1 · Yuchen Wei1 · Wei Wei1 · Lifan Zhang1 · Jie Chen1 Received: 3 May 2020 / Accepted: 14 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract As a momentous post-transcriptional regulator, microRNAs (miRNAs) are attracting more and more attention. The classical miRNAs regulated mechanism shows it binds to the targets’ 3′UTR thus play the role in post-transcription. Meanwhile, single miRNA can target multiple genes, so those should compete to bind that miRNA. Vice versa, single gene can sponge mass of miRNAs as well. Thus the competitive endogenous RNAs (ceRNAs) hypothesis was put forward in 2011. The ceRNA hypothesis has made huge achievements, in particular in non-coding genes, which including long non-coding RNAs (lncRNAs), circle RNAs (circRNAs) and pseudogenes, even viral transcripts. It also contributed greatly to epigenetics development. However, an increasing number of controversies have occurred with applause. Based on this situation, this review introduces something in detail about the ceRNAs hypothesis achieved in lncRNAs, circRNAs, pseudogenes and viral transcripts, respectively. Meanwhile, it also covers controversy of the ceRNAs hypothesis. Keywords miRNA · ceRNA · lncRNA · circRNA · Pseudogene · Controversy
The classical miRNA biogenesis pathway The first microRNA, lin-4, was found in nematode Caenorhabditis elegans before nearly four decades. Originally believed the lin-4 was a protein coding gene; however, the product of lin-4 unexpectedly was a 22-nucleotides regulatory RNA [1–3]. Since then, thousands of miRNAs have been found among kinds of species, including animals, plants, etc. Animal microRNAs are highly conserved among species. There are a mass of conserved and homologous miRNAs even in distinct species, which shows the biological functions of the miRNAs are crucial. The processing of miRNAs contains the following parts: the first step is transcription of primary microRNAs, the second step is splicing of precursor microRNAs, and finally is miRNAs’ maturing, as shown in Fig. 1. First, RNA polymerase II (a few ones are RNA polymerase III) mediates the miRNA genes or introns produce a primary microRNA transcripts (pri-microRNA) with stem-loop
* Jie Chen [email protected] 1
Nanjing Agricultural University, Nanjing, China
structure, and whose length usually is thousands nucleotides [4, 5]. Subsequently, the endonuclease Drosha splices the primicroRNA into precursor microRNA (pre-microRNA) with small hairpin structure, whose length approximately is 65 nucleotides [6–9]. This co-transcriptional mode raises widely consensus. It occurred during the primary transcripts that have not separated with the genome DNA yet. Then the pre-miRNAs are transported from nucleus to cytoplasm in Ran-GTPase-dependent manner by the exportin-5 [10–12]. Processing step occurred in the cytoplasm is essential for pre-miRNAs to become matu
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