A microRNA Arising from the Negative Strand of SARS-CoV-2 Genome Targets FOS to Reduce AP-1 Activity
Virus-encoded microRNAs were first reported in the Epstein–Barr virus in 2004. Subsequently, a few hundred viral miRNAs have been identified, mainly in DNA viruses belonging to the <i>herpesviridae</i> family. To date, only 30 viral miRNAs encoded by RNA viruses are reported by miRBase....
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
|
| Series: | Non-Coding RNA |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2311-553X/9/3/33 |
| _version_ | 1797593267227852800 |
|---|---|
| author | Francesco Greco Elisa Lorefice Claudia Carissimi Ilaria Laudadio Fabiola Ciccosanti Martina Di Rienzo Francesca Colavita Silvia Meschi Fabrizio Maggi Gian Maria Fimia Valerio Fulci |
| author_facet | Francesco Greco Elisa Lorefice Claudia Carissimi Ilaria Laudadio Fabiola Ciccosanti Martina Di Rienzo Francesca Colavita Silvia Meschi Fabrizio Maggi Gian Maria Fimia Valerio Fulci |
| author_sort | Francesco Greco |
| collection | DOAJ |
| description | Virus-encoded microRNAs were first reported in the Epstein–Barr virus in 2004. Subsequently, a few hundred viral miRNAs have been identified, mainly in DNA viruses belonging to the <i>herpesviridae</i> family. To date, only 30 viral miRNAs encoded by RNA viruses are reported by miRBase. Since the outbreak of the SARS-CoV-2 pandemic, several studies have predicted and, in some cases, experimentally validated miRNAs originating from the positive strand of the SARS-CoV-2 genome. By integrating NGS data analysis and qRT-PCR approaches, we found that SARS-CoV-2 also encodes for a viral miRNA arising from the minus (antisense) strand of the viral genome, in the region encoding for ORF1ab, herein referred to as SARS-CoV-2-miR-AS1. Our data show that the expression of this microRNA increases in a time course analysis of SARS-CoV-2 infected cells. Furthermore, enoxacin treatment enhances the accumulation of the mature SARS-CoV-2-miR-AS1 in SARS-CoV-2 infected cells, arguing for a Dicer-dependent processing of this small RNA. In silico analysis suggests that SARS-CoV-2-miR-AS1 targets a set of genes which are translationally repressed during SARS-CoV-2 infection. We experimentally validated that SARS-CoV-2-miR-AS1 targets FOS, thus repressing the AP-1 transcription factor activity in human cells. |
| first_indexed | 2024-03-11T02:05:37Z |
| format | Article |
| id | doaj.art-b926b3451bab48e5b2f41c1ac7340d26 |
| institution | Directory Open Access Journal |
| issn | 2311-553X |
| language | English |
| last_indexed | 2024-03-11T02:05:37Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Non-Coding RNA |
| spelling | doaj.art-b926b3451bab48e5b2f41c1ac7340d262023-11-18T11:54:26ZengMDPI AGNon-Coding RNA2311-553X2023-05-01933310.3390/ncrna9030033A microRNA Arising from the Negative Strand of SARS-CoV-2 Genome Targets FOS to Reduce AP-1 ActivityFrancesco Greco0Elisa Lorefice1Claudia Carissimi2Ilaria Laudadio3Fabiola Ciccosanti4Martina Di Rienzo5Francesca Colavita6Silvia Meschi7Fabrizio Maggi8Gian Maria Fimia9Valerio Fulci10Dipartimento di Medicina Molecolare, Università di Roma “La Sapienza”, 00161 Rome, ItalyDipartimento di Medicina Molecolare, Università di Roma “La Sapienza”, 00161 Rome, ItalyDipartimento di Medicina Molecolare, Università di Roma “La Sapienza”, 00161 Rome, ItalyDipartimento di Medicina Molecolare, Università di Roma “La Sapienza”, 00161 Rome, ItalyDepartment of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases IRCCS ‘L. Spallanzani’, 00149 Rome, ItalyDepartment of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases IRCCS ‘L. Spallanzani’, 00149 Rome, ItalyDepartment of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases IRCCS ‘L. Spallanzani’, 00149 Rome, ItalyDepartment of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases IRCCS ‘L. Spallanzani’, 00149 Rome, ItalyDepartment of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases IRCCS ‘L. Spallanzani’, 00149 Rome, ItalyDipartimento di Medicina Molecolare, Università di Roma “La Sapienza”, 00161 Rome, ItalyDipartimento di Medicina Molecolare, Università di Roma “La Sapienza”, 00161 Rome, ItalyVirus-encoded microRNAs were first reported in the Epstein–Barr virus in 2004. Subsequently, a few hundred viral miRNAs have been identified, mainly in DNA viruses belonging to the <i>herpesviridae</i> family. To date, only 30 viral miRNAs encoded by RNA viruses are reported by miRBase. Since the outbreak of the SARS-CoV-2 pandemic, several studies have predicted and, in some cases, experimentally validated miRNAs originating from the positive strand of the SARS-CoV-2 genome. By integrating NGS data analysis and qRT-PCR approaches, we found that SARS-CoV-2 also encodes for a viral miRNA arising from the minus (antisense) strand of the viral genome, in the region encoding for ORF1ab, herein referred to as SARS-CoV-2-miR-AS1. Our data show that the expression of this microRNA increases in a time course analysis of SARS-CoV-2 infected cells. Furthermore, enoxacin treatment enhances the accumulation of the mature SARS-CoV-2-miR-AS1 in SARS-CoV-2 infected cells, arguing for a Dicer-dependent processing of this small RNA. In silico analysis suggests that SARS-CoV-2-miR-AS1 targets a set of genes which are translationally repressed during SARS-CoV-2 infection. We experimentally validated that SARS-CoV-2-miR-AS1 targets FOS, thus repressing the AP-1 transcription factor activity in human cells.https://www.mdpi.com/2311-553X/9/3/33microRNASARS-CoV-2FOSAP-1SARS-CoV-2-miR-AS1 |
| spellingShingle | Francesco Greco Elisa Lorefice Claudia Carissimi Ilaria Laudadio Fabiola Ciccosanti Martina Di Rienzo Francesca Colavita Silvia Meschi Fabrizio Maggi Gian Maria Fimia Valerio Fulci A microRNA Arising from the Negative Strand of SARS-CoV-2 Genome Targets FOS to Reduce AP-1 Activity Non-Coding RNA microRNA SARS-CoV-2 FOS AP-1 SARS-CoV-2-miR-AS1 |
| title | A microRNA Arising from the Negative Strand of SARS-CoV-2 Genome Targets FOS to Reduce AP-1 Activity |
| title_full | A microRNA Arising from the Negative Strand of SARS-CoV-2 Genome Targets FOS to Reduce AP-1 Activity |
| title_fullStr | A microRNA Arising from the Negative Strand of SARS-CoV-2 Genome Targets FOS to Reduce AP-1 Activity |
| title_full_unstemmed | A microRNA Arising from the Negative Strand of SARS-CoV-2 Genome Targets FOS to Reduce AP-1 Activity |
| title_short | A microRNA Arising from the Negative Strand of SARS-CoV-2 Genome Targets FOS to Reduce AP-1 Activity |
| title_sort | microrna arising from the negative strand of sars cov 2 genome targets fos to reduce ap 1 activity |
| topic | microRNA SARS-CoV-2 FOS AP-1 SARS-CoV-2-miR-AS1 |
| url | https://www.mdpi.com/2311-553X/9/3/33 |
| work_keys_str_mv | AT francescogreco amicrornaarisingfromthenegativestrandofsarscov2genometargetsfostoreduceap1activity AT elisalorefice amicrornaarisingfromthenegativestrandofsarscov2genometargetsfostoreduceap1activity AT claudiacarissimi amicrornaarisingfromthenegativestrandofsarscov2genometargetsfostoreduceap1activity AT ilarialaudadio amicrornaarisingfromthenegativestrandofsarscov2genometargetsfostoreduceap1activity AT fabiolaciccosanti amicrornaarisingfromthenegativestrandofsarscov2genometargetsfostoreduceap1activity AT martinadirienzo amicrornaarisingfromthenegativestrandofsarscov2genometargetsfostoreduceap1activity AT francescacolavita amicrornaarisingfromthenegativestrandofsarscov2genometargetsfostoreduceap1activity AT silviameschi amicrornaarisingfromthenegativestrandofsarscov2genometargetsfostoreduceap1activity AT fabriziomaggi amicrornaarisingfromthenegativestrandofsarscov2genometargetsfostoreduceap1activity AT gianmariafimia amicrornaarisingfromthenegativestrandofsarscov2genometargetsfostoreduceap1activity AT valeriofulci amicrornaarisingfromthenegativestrandofsarscov2genometargetsfostoreduceap1activity AT francescogreco micrornaarisingfromthenegativestrandofsarscov2genometargetsfostoreduceap1activity AT elisalorefice micrornaarisingfromthenegativestrandofsarscov2genometargetsfostoreduceap1activity AT claudiacarissimi micrornaarisingfromthenegativestrandofsarscov2genometargetsfostoreduceap1activity AT ilarialaudadio micrornaarisingfromthenegativestrandofsarscov2genometargetsfostoreduceap1activity AT fabiolaciccosanti micrornaarisingfromthenegativestrandofsarscov2genometargetsfostoreduceap1activity AT martinadirienzo micrornaarisingfromthenegativestrandofsarscov2genometargetsfostoreduceap1activity AT francescacolavita micrornaarisingfromthenegativestrandofsarscov2genometargetsfostoreduceap1activity AT silviameschi micrornaarisingfromthenegativestrandofsarscov2genometargetsfostoreduceap1activity AT fabriziomaggi micrornaarisingfromthenegativestrandofsarscov2genometargetsfostoreduceap1activity AT gianmariafimia micrornaarisingfromthenegativestrandofsarscov2genometargetsfostoreduceap1activity AT valeriofulci micrornaarisingfromthenegativestrandofsarscov2genometargetsfostoreduceap1activity |