An RNA Metabolism and Surveillance Quartet in the Major Histocompatibility Complex
At the central region of the mammalian major histocompatibility complex (MHC) is a complement gene cluster that codes for constituents of complement C3 convertases (C2, factor B and C4). Complement activation drives the humoral effector functions for immune response. Sandwiched between the genes for...
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MDPI AG
2019-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/9/1008 |
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| author | Danlei Zhou Michalea Lai Aiqin Luo Chack-Yung Yu |
| author_facet | Danlei Zhou Michalea Lai Aiqin Luo Chack-Yung Yu |
| author_sort | Danlei Zhou |
| collection | DOAJ |
| description | At the central region of the mammalian major histocompatibility complex (MHC) is a complement gene cluster that codes for constituents of complement C3 convertases (C2, factor B and C4). Complement activation drives the humoral effector functions for immune response. Sandwiched between the genes for serine proteinase factor B and anchor protein C4 are four less known but critically important genes coding for essential functions related to metabolism and surveillance of RNA during the transcriptional and translational processes of gene expression. These four genes are NELF-E (RD), SKIV2L (SKI2W), DXO (DOM3Z) and STK19 (RP1 or G11) and dubbed as NSDK. NELF-E is the subunit E of negative elongation factor responsible for promoter proximal pause of transcription. SKIV2L is the RNA helicase for cytoplasmic exosomes responsible for degradation of de-polyadenylated mRNA and viral RNA. DXO is a powerful enzyme with pyro-phosphohydrolase activity towards 5′ triphosphorylated RNA, decapping and exoribonuclease activities of faulty nuclear RNA molecules. STK19 is a nuclear kinase that phosphorylates RNA-binding proteins during transcription. STK19 is also involved in DNA repair during active transcription and in nuclear signal transduction. The genetic, biochemical and functional properties for NSDK in the MHC largely stay as a secret for many immunologists. Here we briefly review the roles of (a) NELF-E on transcriptional pausing; (b) SKIV2L on turnover of deadenylated or expired RNA 3′→5′ through the Ski-exosome complex, and modulation of inflammatory response initiated by retinoic acid-inducible gene 1-like receptor (RLR) sensing of viral infections; (c) DXO on quality control of RNA integrity through recognition of 5′ caps and destruction of faulty adducts in 5′→3′ fashion; and (d) STK19 on nuclear protein phosphorylations. There is compelling evidence that a dysregulation or a deficiency of a NSDK gene would cause a malignant, immunologic or digestive disease. |
| first_indexed | 2024-03-12T20:07:04Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T20:07:04Z |
| publishDate | 2019-08-01 |
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| series | Cells |
| spelling | doaj.art-bbce4643f0f44144a5a90b4020fabf2b2023-08-02T02:03:40ZengMDPI AGCells2073-44092019-08-0189100810.3390/cells8091008cells8091008An RNA Metabolism and Surveillance Quartet in the Major Histocompatibility ComplexDanlei Zhou0Michalea Lai1Aiqin Luo2Chack-Yung Yu3School of Life Science, Beijing Institute of Technology, Beijing 100081, ChinaThe Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USASchool of Life Science, Beijing Institute of Technology, Beijing 100081, ChinaThe Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USAAt the central region of the mammalian major histocompatibility complex (MHC) is a complement gene cluster that codes for constituents of complement C3 convertases (C2, factor B and C4). Complement activation drives the humoral effector functions for immune response. Sandwiched between the genes for serine proteinase factor B and anchor protein C4 are four less known but critically important genes coding for essential functions related to metabolism and surveillance of RNA during the transcriptional and translational processes of gene expression. These four genes are NELF-E (RD), SKIV2L (SKI2W), DXO (DOM3Z) and STK19 (RP1 or G11) and dubbed as NSDK. NELF-E is the subunit E of negative elongation factor responsible for promoter proximal pause of transcription. SKIV2L is the RNA helicase for cytoplasmic exosomes responsible for degradation of de-polyadenylated mRNA and viral RNA. DXO is a powerful enzyme with pyro-phosphohydrolase activity towards 5′ triphosphorylated RNA, decapping and exoribonuclease activities of faulty nuclear RNA molecules. STK19 is a nuclear kinase that phosphorylates RNA-binding proteins during transcription. STK19 is also involved in DNA repair during active transcription and in nuclear signal transduction. The genetic, biochemical and functional properties for NSDK in the MHC largely stay as a secret for many immunologists. Here we briefly review the roles of (a) NELF-E on transcriptional pausing; (b) SKIV2L on turnover of deadenylated or expired RNA 3′→5′ through the Ski-exosome complex, and modulation of inflammatory response initiated by retinoic acid-inducible gene 1-like receptor (RLR) sensing of viral infections; (c) DXO on quality control of RNA integrity through recognition of 5′ caps and destruction of faulty adducts in 5′→3′ fashion; and (d) STK19 on nuclear protein phosphorylations. There is compelling evidence that a dysregulation or a deficiency of a NSDK gene would cause a malignant, immunologic or digestive disease.https://www.mdpi.com/2073-4409/8/9/1008DXODOM3ZNELF-ERDSKIV2LSKI2WSTK19RP1NSDKRLRmiR1236SVARNA quality control5′→3′ RNA decay3′→5′ mRNA turnoverantiviral immunityinterferon βpromoter-proximal transcriptional pauseexosomesnuclear kinasehepatocellular carcinomaSki complextrichohepatoenteric syndromemelanoma |
| spellingShingle | Danlei Zhou Michalea Lai Aiqin Luo Chack-Yung Yu An RNA Metabolism and Surveillance Quartet in the Major Histocompatibility Complex Cells DXO DOM3Z NELF-E RD SKIV2L SKI2W STK19 RP1 NSDK RLR miR1236 SVA RNA quality control 5′→3′ RNA decay 3′→5′ mRNA turnover antiviral immunity interferon β promoter-proximal transcriptional pause exosomes nuclear kinase hepatocellular carcinoma Ski complex trichohepatoenteric syndrome melanoma |
| title | An RNA Metabolism and Surveillance Quartet in the Major Histocompatibility Complex |
| title_full | An RNA Metabolism and Surveillance Quartet in the Major Histocompatibility Complex |
| title_fullStr | An RNA Metabolism and Surveillance Quartet in the Major Histocompatibility Complex |
| title_full_unstemmed | An RNA Metabolism and Surveillance Quartet in the Major Histocompatibility Complex |
| title_short | An RNA Metabolism and Surveillance Quartet in the Major Histocompatibility Complex |
| title_sort | rna metabolism and surveillance quartet in the major histocompatibility complex |
| topic | DXO DOM3Z NELF-E RD SKIV2L SKI2W STK19 RP1 NSDK RLR miR1236 SVA RNA quality control 5′→3′ RNA decay 3′→5′ mRNA turnover antiviral immunity interferon β promoter-proximal transcriptional pause exosomes nuclear kinase hepatocellular carcinoma Ski complex trichohepatoenteric syndrome melanoma |
| url | https://www.mdpi.com/2073-4409/8/9/1008 |
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