Characterization of epitranscriptome reader proteins experimentally and in silico: Current knowledge and future perspectives beyond the YTH domain
To date, over 150 chemical modifications to the four canonical RNA bases have been discovered, known collectively as the epitranscriptome. Many of these modifications have been implicated in a variety of cellular processes and disease states. Additional work has been done to identify proteins known...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Computational and Structural Biotechnology Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037023002313 |
| _version_ | 1797384107747966976 |
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| author | Lucas G. Miller Madeline Demny Phanourios Tamamis Lydia M. Contreras |
| author_facet | Lucas G. Miller Madeline Demny Phanourios Tamamis Lydia M. Contreras |
| author_sort | Lucas G. Miller |
| collection | DOAJ |
| description | To date, over 150 chemical modifications to the four canonical RNA bases have been discovered, known collectively as the epitranscriptome. Many of these modifications have been implicated in a variety of cellular processes and disease states. Additional work has been done to identify proteins known as “readers” that selectively interact with RNAs that contain specific chemical modifications. Protein interactomes with N6-methyladenosine (m6A), N1-methyladenosine (m1A), N5-methylcytosine (m5C), and 8-oxo-7,8-dihydroguanosine (8-oxoG) have been determined, mainly through experimental advances in proteomics techniques. However, relatively few proteins have been confirmed to bind directly to RNA containing these modifications. Furthermore, for many of these protein readers, the exact binding mechanisms as well as the exclusivity for recognition of modified RNA species remain elusive, leading to questions regarding their roles within different cellular processes. In the case of the YT-521B homology (YTH) family of proteins, both experimental and in silico techniques have been leveraged to provide valuable biophysical insights into the mechanisms of m6A recognition at atomic resolution. To date, the YTH family is one of the best characterized classes of readers. Here, we review current knowledge about epitranscriptome recognition of the YTH domain proteins from previously published experimental and computational studies. We additionally outline knowledge gaps for proteins beyond the well-studied human YTH domains and the current in silico techniques and resources that can enable investigation of protein interactions with modified RNA outside of the YTH-m6A context. |
| first_indexed | 2024-03-08T21:30:43Z |
| format | Article |
| id | doaj.art-f948873b2c504038b7a63cab23b00912 |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-03-08T21:30:43Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-f948873b2c504038b7a63cab23b009122023-12-21T07:31:42ZengElsevierComputational and Structural Biotechnology Journal2001-03702023-01-012135413556Characterization of epitranscriptome reader proteins experimentally and in silico: Current knowledge and future perspectives beyond the YTH domainLucas G. Miller0Madeline Demny1Phanourios Tamamis2Lydia M. Contreras3McKetta Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USAArtie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX, USAArtie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX, USA; Department of Materials Science & Engineering, Texas A&M University, College Station, TX, USA; Correspondence to: Artie McFerrin Department of Chemical Engineering, Jack E. Brown Chemical Engineering Building, 3122 TAMU, 100 Spence St., College Station, TX 77843, USA.McKetta Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA; Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX, USA; Correspondence to: McKetta Department of Chemical Engineering, 200 E. Dean Keeton St., Stop C0400, Austin, TX 78712, USA.To date, over 150 chemical modifications to the four canonical RNA bases have been discovered, known collectively as the epitranscriptome. Many of these modifications have been implicated in a variety of cellular processes and disease states. Additional work has been done to identify proteins known as “readers” that selectively interact with RNAs that contain specific chemical modifications. Protein interactomes with N6-methyladenosine (m6A), N1-methyladenosine (m1A), N5-methylcytosine (m5C), and 8-oxo-7,8-dihydroguanosine (8-oxoG) have been determined, mainly through experimental advances in proteomics techniques. However, relatively few proteins have been confirmed to bind directly to RNA containing these modifications. Furthermore, for many of these protein readers, the exact binding mechanisms as well as the exclusivity for recognition of modified RNA species remain elusive, leading to questions regarding their roles within different cellular processes. In the case of the YT-521B homology (YTH) family of proteins, both experimental and in silico techniques have been leveraged to provide valuable biophysical insights into the mechanisms of m6A recognition at atomic resolution. To date, the YTH family is one of the best characterized classes of readers. Here, we review current knowledge about epitranscriptome recognition of the YTH domain proteins from previously published experimental and computational studies. We additionally outline knowledge gaps for proteins beyond the well-studied human YTH domains and the current in silico techniques and resources that can enable investigation of protein interactions with modified RNA outside of the YTH-m6A context.http://www.sciencedirect.com/science/article/pii/S2001037023002313EpitranscriptomicsRNA binding proteinsYT-521B Homology (YTH) protein familyMolecular dynamics (MD) simulationsAlphaFoldProtein Structure Database |
| spellingShingle | Lucas G. Miller Madeline Demny Phanourios Tamamis Lydia M. Contreras Characterization of epitranscriptome reader proteins experimentally and in silico: Current knowledge and future perspectives beyond the YTH domain Computational and Structural Biotechnology Journal Epitranscriptomics RNA binding proteins YT-521B Homology (YTH) protein family Molecular dynamics (MD) simulations AlphaFold Protein Structure Database |
| title | Characterization of epitranscriptome reader proteins experimentally and in silico: Current knowledge and future perspectives beyond the YTH domain |
| title_full | Characterization of epitranscriptome reader proteins experimentally and in silico: Current knowledge and future perspectives beyond the YTH domain |
| title_fullStr | Characterization of epitranscriptome reader proteins experimentally and in silico: Current knowledge and future perspectives beyond the YTH domain |
| title_full_unstemmed | Characterization of epitranscriptome reader proteins experimentally and in silico: Current knowledge and future perspectives beyond the YTH domain |
| title_short | Characterization of epitranscriptome reader proteins experimentally and in silico: Current knowledge and future perspectives beyond the YTH domain |
| title_sort | characterization of epitranscriptome reader proteins experimentally and in silico current knowledge and future perspectives beyond the yth domain |
| topic | Epitranscriptomics RNA binding proteins YT-521B Homology (YTH) protein family Molecular dynamics (MD) simulations AlphaFold Protein Structure Database |
| url | http://www.sciencedirect.com/science/article/pii/S2001037023002313 |
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