The new regulatory role of long non-coded RNA.

Biotechnology Channel News: This year's "China Young Women Scientists Award" has been announced, from the Chinese Academy of Sciences Institute of Biomedical and Cell Researcher Chen Lingling and other 10 young female science and technology workers from 111 units nominated by 216 valid candidates, was awarded the "China Young Women Scientists Award."
Among them, researchers chen Lingling have long been engaged in the human genome of "dark matter" - long non-coded RNA (IncRNA) research, to explore their key role in normal life activities, as well as the disease small fat Willie disease, cancer and other developments.
May 5, the internationally renowned academic journal Cell magazine published the latest research results of chen Lingling's research team on long non-coding RNA: "SLERT regulations DDX21-rings associated with Pol I Pol Iion", which reveals the important role of long non-coding RNA SLERT in cellular kernel function and RNA polymerase I (Pol I) transcription process.
human cells contain about 400 copies of the nuclear glycosome DNA (rDNA) sequence, distributed on five chromosomes, and these areas containing rDNA sequences are called nucleosphere regions (nucleolar organizing region, NOR).
kernels around NOR and are important sites for RNA polymerase I transcription of RNA (rRNA) and rRNA processing.
rhRNA transcription disorders are closely related to disease.
rRNA transcription means that the RNA is dysgenes, which can lead to bone marrow failure anemia, while excessive rRNA transcription is prone to multiple cancers.
because rDNA sequences are highly repetitive, it is still unknown how differences in rDNA expressions on these sequences are implemented and related Pol I transcription regulation mechanisms are available.
classical long non-coding RNA and mRNA structure similar, containing 5' end hat and 3' end poly adenosine tail structure, widely involved in the regulation of various important life activities.
In addition, recently, Chen Lingling's research team and other international researchers have found that there are a series of long non-coding RNA molecular families with special structures in mammalian cells, such as lncRNAs and ring RNAs with special structures of small nucleoRNA (snoRNA), and have important regulatory functions.
this study, using pre-created full transcriptional group sequencing and analysis of poly(A) tail RNA, found a new lncRNA from the sub-region of the human protein-coding gene TBRG4, whose molecular ends contain snoRNA structures and facilitate transcription of ribosome RNA prebodies (pre-rRNA), hence the name SlerT (snoRNA-end lnc RNA).
study found that SLERT comes from a variable shear of tbrg4 pre-mRNA and is positioned in the nucleus (illustrated).
using CRISPR/CAS9 technology to precisely knock out SLERT, the researchers found that the absence of SLERT led to a decrease in Pol I transcription activity.
further studies have found that SLERT can be combined with RNA anti-spinase DDX21.
researchers made a detailed and detailed look at the positioning of DDX21 in cell nuclei using structural lighting microtechnology (STRUCTURE Illumination Microscopy, SIM), and for the first time found that DDX21 surrounds the Pol I complex in the cell nuclei, forming a ring structure with a diameter of about 400nm (illustrated).
interesting is that the formation of this ring structure is coupled with Pol I transcription and inhibits Pol transcription.
in-depth studies have shown that the binding of SLERT to DDX21 can change the protein composition of DDX21, thereby adjusting the rules of the DDX21 ring in the cell nucleus, and ultimately by removing the inhibition of the DDX21 ring on Pol I to play a positive regulation of Pol I transcription function.
it's worth noting that the researchers also found that SLERT knockout inhibited in-body tumorization in mice, a finding that also provided a new target for tumor-targeted therapy for pre-rRNA transcription.
this study is the first to find long non-coding RNA in human cells that regulate Pol I transcription, and explains the distinctive function of this RNA, expanding the mechanism of action of long non-coding RNA.
the study analyzed the molecular mechanisms of rDNA, DDX21 ring, RNA polymerase I, SLERT, and pre-rRNA, and revealed that the size of the DDX21 ring is different for Pol I. The regulatory mechanism of transcription (illustrated) and the control of DDX21 ring by SLERT-DDX21 ring propose a mechanism to regulate Pol I transcription through SLERT-DDX21 ring and control the difference expression of rDNA.
the new mechanism of Pol I transcription from a new perspective, and also provides a new direction for further study of the structure and function of nuclear kernels.
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