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      headline:METTL16 exerts an m6A-independent function to facilitate translation and tumorigenesis
      description:METTL16 has recently been identified as an RNA methyltransferase responsible for the deposition of N6-methyladenosine (m6A) in a few transcripts. Whether METTL16 methylates a large set of transcripts, similar to METTL3 and METTL14, remains unclear. Here we show that METTL16 exerts both methyltransferase activity-dependent and -independent functions in gene regulation. In the cell nucleus, METTL16 functions as an m6A writer to deposit m6A into hundreds of its specific messenger RNA targets. In the cytosol, METTL16 promotes translation in an m6A-independent manner. More specifically, METTL16 directly interacts with the eukaryotic initiation factors 3a and -b as well as ribosomal RNA through its Mtase domain, thereby facilitating the assembly of the translation-initiation complex and promoting the translation of over 4,000 mRNA transcripts. Moreover, we demonstrate that METTL16 is critical for the tumorigenesis of hepatocellular carcinoma. Collectively, our studies reveal previously unappreciated dual functions of METTL16 as an m6A writer and a translation-initiation facilitator, which together contribute to its essential function in tumorigenesis. Su et al. report that while METTL16 acts as an m6A writer in the nucleus, it exerts an m6A-independent function in the cytosol, where it facilitates translation through direct interactions with ribosomal RNAs and eukaryotic initiation factors 3a and -b.
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      affiliation:
            name:Beckman Research Institute of City of Hope
            address:
               name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
               type:PostalAddress
            type:Organization
      name:Chao Shen
      affiliation:
            name:Beckman Research Institute of City of Hope
            address:
               name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
               type:PostalAddress
            type:Organization
      name:Meilin Xue
      affiliation:
            name:Beckman Research Institute of City of Hope
            address:
               name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
               type:PostalAddress
            type:Organization
      name:Keren Zhou
      affiliation:
            name:Beckman Research Institute of City of Hope
            address:
               name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
               type:PostalAddress
            type:Organization
      name:Zhenhua Chen
      affiliation:
            name:Beckman Research Institute of City of Hope
            address:
               name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
               type:PostalAddress
            type:Organization
      name:Jianhuang Xue
      affiliation:
            name:Beckman Research Institute of City of Hope
            address:
               name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
               type:PostalAddress
            type:Organization
      name:Wei Li
      affiliation:
            name:Beckman Research Institute of City of Hope
            address:
               name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
               type:PostalAddress
            type:Organization
      name:Hanjun Qin
      affiliation:
            name:Beckman Research Institute of City of Hope
            address:
               name:The Integrative Genomics Core, Beckman Research Institute of City of Hope, Duarte, USA
               type:PostalAddress
            type:Organization
      name:Xiwei Wu
      affiliation:
            name:Beckman Research Institute of City of Hope
            address:
               name:The Integrative Genomics Core, Beckman Research Institute of City of Hope, Duarte, USA
               type:PostalAddress
            type:Organization
      name:Miao Sun
      affiliation:
            name:Children’s Hospital Los Angeles
            address:
               name:Keck School of Medicine, University of Southern California, and Department of Pathology and Laboratory Medicine, Children’s Hospital Los Angeles, Los Angeles, USA
               type:PostalAddress
            type:Organization
      name:Yunsun Nam
      url:http://orcid.org/0000-0002-7939-8626
      affiliation:
            name:University of Texas Southwestern Medical Center
            address:
               name:Laboratory of RNA Biology, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, USA
               type:PostalAddress
            type:Organization
      name:Chun-Wei Chen
      url:http://orcid.org/0000-0002-8737-6830
      affiliation:
            name:Beckman Research Institute of City of Hope
            address:
               name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
               type:PostalAddress
            type:Organization
            name:City of Hope
            address:
               name:City of Hope Comprehensive Cancer Center, City of Hope, Duarte, USA
               type:PostalAddress
            type:Organization
      name:Wendong Huang
      url:http://orcid.org/0000-0003-3735-9466
      affiliation:
            name:Beckman Research Institute of City of Hope
            address:
               name:Department of Diabetes Complications and Metabolism, Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, USA
               type:PostalAddress
            type:Organization
            name:City of Hope
            address:
               name:Graduate School of Biological Science, City of Hope, Duarte, USA
               type:PostalAddress
            type:Organization
      name:David Horne
      affiliation:
            name:City of Hope
            address:
               name:City of Hope Comprehensive Cancer Center, City of Hope, Duarte, USA
               type:PostalAddress
            type:Organization
            name:Beckman Research Institute of City of Hope
            address:
               name:Department of Molecular Medicine, Beckman Research Institute of City of Hope, Duarte, USA
               type:PostalAddress
            type:Organization
      name:Steven T. Rosen
      affiliation:
            name:City of Hope
            address:
               name:City of Hope Comprehensive Cancer Center, City of Hope, Duarte, USA
               type:PostalAddress
            type:Organization
            name:City of Hope
            address:
               name:Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, USA
               type:PostalAddress
            type:Organization
            name:City of Hope
            address:
               name:Gehr Family Center for Leukemia Research, City of Hope, Duarte, USA
               type:PostalAddress
            type:Organization
      name:Chuan He
      url:http://orcid.org/0000-0003-4319-7424
      affiliation:
            name:The University of Chicago
            address:
               name:Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, USA
               type:PostalAddress
            type:Organization
            name:The University of Chicago
            address:
               name:Howard Hughes Medical Institute, The University of Chicago, Chicago, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Jianjun Chen
      url:http://orcid.org/0000-0003-3749-2902
      affiliation:
            name:Beckman Research Institute of City of Hope
            address:
               name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
               type:PostalAddress
            type:Organization
            name:City of Hope
            address:
               name:City of Hope Comprehensive Cancer Center, City of Hope, Duarte, USA
               type:PostalAddress
            type:Organization
            name:City of Hope
            address:
               name:Gehr Family Center for Leukemia Research, City of Hope, Duarte, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
      name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
      name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
      name:Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
      name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
      name:Department of Pharmaceutics, School of Pharmaceutical Science, Jiangnan University, Wuxi, China
      name:Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, USA
      name:Howard Hughes Medical Institute, The University of Chicago, Chicago, USA
      name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
      name:Department of Immunology, Hebei Medical University, Shijiazhuang, China
      name:Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, USA
      name:Howard Hughes Medical Institute, The University of Chicago, Chicago, USA
      name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
      name:Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
      name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
      name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
      name:School of Pharmacy, China Medical University, Shenyang, China
      name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
      name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
      name:Key Laboratory of Hematopoietic Malignancies, The First Affiliated Hospital of Zhejiang University, Hangzhou, China
      name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
      name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
      name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
      name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
      name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
      name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
      name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
      name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
      name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
      name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
      name:The Integrative Genomics Core, Beckman Research Institute of City of Hope, Duarte, USA
      name:The Integrative Genomics Core, Beckman Research Institute of City of Hope, Duarte, USA
      name:Keck School of Medicine, University of Southern California, and Department of Pathology and Laboratory Medicine, Children’s Hospital Los Angeles, Los Angeles, USA
      name:Laboratory of RNA Biology, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, USA
      name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
      name:City of Hope Comprehensive Cancer Center, City of Hope, Duarte, USA
      name:Department of Diabetes Complications and Metabolism, Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, USA
      name:Graduate School of Biological Science, City of Hope, Duarte, USA
      name:City of Hope Comprehensive Cancer Center, City of Hope, Duarte, USA
      name:Department of Molecular Medicine, Beckman Research Institute of City of Hope, Duarte, USA
      name:City of Hope Comprehensive Cancer Center, City of Hope, Duarte, USA
      name:Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, USA
      name:Gehr Family Center for Leukemia Research, City of Hope, Duarte, USA
      name:Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, USA
      name:Howard Hughes Medical Institute, The University of Chicago, Chicago, USA
      name:Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, USA
      name:City of Hope Comprehensive Cancer Center, City of Hope, Duarte, USA
      name:Gehr Family Center for Leukemia Research, City of Hope, Duarte, USA
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Mail Servers:

• mxa-002c5801.gslb.pphosted.com
• mxb-002c5801.gslb.pphosted.com

Name Servers:

• pdns1.ultradns.net
• pdns2.ultradns.net
• pdns3.ultradns.org
• pdns4.ultradns.org
• pdns5.ultradns.info
• pdns6.ultradns.co.uk

CDN Services {📦}

• Crossref