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- Table of Contents
Facts about 5'-3' exoribonuclease 2.
During transcription termination, cleavage at the polyadenylation site liberates a 5' fragment that is then processed to form the mature mRNA and a 3' fragment which remains attached to the elongating polymerase. The processive degradation of this 3' fragment at this protein can promote termination of transcription.
Human | |
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Gene Name: | XRN2 |
Uniprot: | Q9H0D6 |
Entrez: | 22803 |
Belongs to: |
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5'-3' exonuclease family |
5'-3' exoribonuclease 2; Dhm1-like protein (mouse homolog); DHM1-like protein; DHP protein; EC 3.1.13; EC 3.1.13.-
Mass (kDA):
108.582 kDA
Human | |
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Location: | 20p11.22 |
Sequence: | 20; NC_000020.11 (21303313..21389825) |
Expressed in the spleen, thymus, prostate, testis, ovary, small intestine, colon, peripheral blood leukocytes, heart, brain, placenta, lung, liver, skeletal muscle, kidney, and pancreas. Isoform 2 is expressed predominantly in peripheral blood leukocytes.
Nucleus, nucleolus.
XRN2 is a protein that plays a role in gene silencing and RNA metabolism. This article explores the function of XRN2 and how it is associated with novel proteins. This article also discusses the importance of RNA metabolism and gene silencing. You will learn how this protein can aid in the research process. Its role in gene silencing is one of the most intriguing questions in modern biology.
The Anti-5'-3' exoribonuclease 2 XRN2 Antibody is a versatile, highly specific reagent for the investigation of the RNA processing enzyme XRN2. This monoclonal antibody reacts with human, Mouse, Monkey and yeast. It also detects a broad range of other proteins, including GAPDH. It was originally discovered to be a component of the rixosome, a multienzyme complex that is essential in ribosomal RNA processing and biogenesis. Its endonuclease subunit cleaves within rRNA's internal transcribed spacer 2. The polynuclease kinase subunit phosphorylates the precursor to allow XRN2-mediated trimming of rRNAs.
XRN2 is a co-enzyme that functions with the RNA endonuclease LAS1L and the polynucleotide kinase NOL9. These subunits cooperate to degrade RNA at polycomb target loci in human cells. When XRN2 is degraded, a 5'-OH group is generated, which needs to be phosphorylated by the NOL9 polynucleotide kinase.
Using a genomic approach, we have detected XRN2 association with the novel protein H2AK119ub1 at PCDh20 gene. These data indicate that XRN2 may be involved in the processing of RNA by polycomb repressive complex. The results show that XRN2 and H2AK119ub1 cooperate to degrade RNA from Polycomb target loci.
Cells were cultured with siRNA targeting each of the two proteins. Then, their sensitivity to a-amanitin was determined using a colony-forming assay. Depletion of FUS or TDP43 increased the sensitivity to a-amanitin, indicating that loss of function of either protein would lead to defective repair or prevention of transcription arrest-associated DNA damage.
In a separate experiment, we also identified H2AK119ub1 and PCDh20 as enriched ECs. The data were further analysed using quantitative label-free mass spectrometry. We also identified the H2AK119ub1 and H3K27me3 modifications among enriched genes. After performing this analysis, we calculated P-values and Mann-Whitney tests.
XRN2 is associated with a number of transcription elongation factors that were found at the 5' region of the gene. These include the mRNA capping complex, Paf1 complex, and Spt4/5 complex. These proteins have been implicated in the early stages of productive elongation in yeast and mammals. This data will enable us to determine the role of XRN2 in early transcription dynamics near promoter proximal pause sites.
The XRN2 family of nucleases has a multitude of roles in the cell, including RNA metabolism. This RNA degradation enzyme is critical for the processing and turnover of fundamentally important RNAs, including transcripts of H3K27me3-marked genes. The activities of the various members of the XRN family are well documented, and several new functions have been discovered. Here, we will discuss the role of XRN2 in RNA metabolism and the mechanisms involved in its function.
One important role of XRN2 in RNA metabolism is to help regulate PARP1 and RNA decay. Inhibitors of PARP1 inhibit XRN2, resulting in a reduction in RNA levels. This inhibition also inhibits PARP1. Inhibition of PARP1 is another strategy for targeting XRN2 in cancer. But what exactly is PARP1 inhibition? This enzyme is required for PARP1 metabolism.
To perform this function, XRN-2 must bind to miRNA. XRN-2 interacts with the miRNA by catalysis through an acid-base mechanism. This interaction induces conformational changes in XRN-2, which increases its stability. Moreover, miRNA binding increases the stability of XRN-2 by bringing critical residues closer together. This results in robust degradation of miRNAs by recombinant XRN-2.
XRN-2 has a dual enzymatic activity, which makes it a versatile enzyme that has the potential to shape the miRNA landscape of dauer organisms. While its miRNA-targeting activity does not play a role in worms that are constantly growing, it is essential for the generation of mature ribosomal RNAs which are required for translation and survival. It has recently been discovered that XRN2 is required in both metabolic pathways.
In addition to regulating gene expression, XRN2 plays a role in plant-specific RNA synthesis. This mechanism helps to prevent genes from being transcribed by antisense transcripts. This mechanism also protects genes from being silenced by read-through transcripts, which may decrease the activity of gene promoters. However, the XRN2 role in plant gene silencing remains unclear.
XRN2 is a highly conserved protein involved in RNA metabolism. It has been linked to DNA replication, cell cycle, and rRNA maturation. This involvement highlights its importance in the cell cycle. Additionally, XRN2 acts as a co-activator of PARP1, a transcription termination enzyme. In humans, XRN2 is involved in RNA metabolism and RNA processing, and has been implicated in gene silencing.
This study also reveals that XRN2 is involved in the control of chromosomal replication, which is crucial for maintaining genetic stability. Moreover, XRN2 interacts with DNA damage-induced proteins, such as PRP19 and RPA1. Further, the XRN2 protein binds to ssDNA-coated RPA, suggesting that these two proteins are intimately linked.
Moreover, XRN2 has associations with novel protein partners involved in diverse cellular processes. Moreover, XRN2 depletion is associated with decreased PAR activity. XRN2 alterations are associated with PARP1 inhibition, which is a possible target in cancer. Inhibiting PARP1 in cancer cells may therefore have important clinical applications. It may also be useful for the development of a new drug targeting XRN2.
Moreover, in a study that examined the DSB repair kinetics in XRN2-deficient cells, R-loop formation was detected in shXRN2 and shScr fibroblasts. Immunofluorescence and a-aman treatments of shXRN2 and shScr fibroblasts were used to monitor the expression of 53BP1.
The XRN2 protein is an important player in transcription termination. It is recruited to transcription sites by hnRNPK and regulates the co-transcriptional degradation of poly(A)-downstream RNA. XRN2 may also be involved in modulating polymerase transcription rates, which may influence their position at the termination site. This study highlights the importance of hnRNPK in XRN2 recruitment.
XRN2 is a highly conserved protein involved in processing downstream cleaved RNA-associated RNA and in the co-transcriptional degradation of aberrant pre-mRNA. It physically interacts with pre-mRNA 3' processing factors, including p53(nrb) and PSF, to mediate transcription termination. In addition, it interacts with a protein known as Kub5-Hera, which facilitates the degradation of aberrant pre-mRNA.
A possible mechanism for XRN2 to inhibit Pol II activity is that it locates near Pol II to prevent redundant 5'-3' exonucleases from accessing nascent RNA. Molecular biochemical studies suggest that Xrn2 may also inhibit Pol II termination by blocking access of redundant 5'-3' exonucleases. Furthermore, Xrn2 depletion induces a termination defect in most protein-coding genes.
However, the molecular mechanisms underlying the effects of XRN2 remain poorly understood. More studies are required to understand the mechanism by which XRN2 affects transcription termination. These differences in XRN2 activity may be variations of the same termination process, or represent distinct processes. However, these findings indicate that XRN2 functions as an integral part of many biological processes. In addition to regulating gene expression and the cell cycle, XRN2 is involved in DNA metabolism and chromosomal replication, a crucial step in the development of cancer.
Moreover, Xrn2 depletion limits the extent of PAS cleavage downstream of the transcription start site. However, it also promotes termination by other mechanisms. CPSF73 inactivation partially impairs the formation of CPSF complexes. Therefore, depletion of Xrn2 may reduce pol II elongation downstream of the TSS. And the effect of Xrn2 depletion is similar to that seen with TTF2 knockdown.
PMID: 10409438 by Zhang M., et al. Cloning and mapping of the XRN2 gene to human chromosome 20p11.1- p11.2.
PMID: 16147866 by Li J., et al. A novel splice variant of human XRN2 gene is mainly expressed in blood leukocyte.