TY - JOUR
T1 - Comparative genetics
T2 - Systematic discovery of cap-independent translation sequences in human and viral genomes
AU - Weingarten-Gabbay, Shira
AU - Elias-Kirma, Shani
AU - Nir, Ronit
AU - Gritsenko, Alexey A.
AU - Stern-Ginossar, Noam
AU - Yakhini, Zohar
AU - Weinberger, Adina
AU - Segal, Eran
N1 - NIH; European Research Council (ERC); Clore Ph.D. fellowship; Kahn Center for Systems Biology; Azrieli Center for Systems BiologyWe gratefully acknowledge N. Rahm and A. Telenti for the lentiviral bicistronic constructs. We are grateful to the Alon lab for the help with tissue culture setting and the Kimchi lab for the help with luciferase assays. We thank M. Levo for fruitful discussions; S. Lubliner for assisting with the design of the library; E. Sharon and Y. Kalma for the help with the high-throughput reporter assay; and Y. Peleg, M. David, M. Selitrennik, H. Sinvani, and T. Danon for help in experimental procedures. S.W.G. is the recipient of the Clore Ph.D. fellowship. This work was supported by grants from the NIH and the European Research Council (ERC) to E. S. and student research grants from the Kahn Center for Systems Biology to S.W.G. and the Azrieli Center for Systems Biology to S.W.G. and S.E.K. Data are deposited in Gene Expression Omnibus (GEO) under accession number GSE74277. Author contributions: S.W.G. concieved the project and devised the experiments, designed the synthetic library, performed experiments, analyzed the data and wrote the manuscript; S.E.K. designed the synthetic library and performed experiments; R.N. performed experiments and provided critical comments on the manuscript; A.A.G performed analyses; N.S.G. performed experiments; Z.Y. contributed to the design and analyses; A.W. contributed to the experimental setting; and E. S. conceived the project, supervised the analyses, and wrote the manuscript. We gratefully acknowledge N. Rahm and A. Telenti for the lentiviral bicistronic constructs. We are grateful to the Alon lab for the help with tissue culture setting and the Kimchi lab for the help with luciferase assays. We thank M. Levo for fruitful discussions; S. Lubliner for assisting with the design of the library; E. Sharon and Y. Kalma for the help with the high-throughput reporter assay; and Y. Peleg, M. David, M. Selitrennik, H. Sinvani, and T. Danon for help in experimental procedures. S.W.G. is the recipient of the Clore Ph.D. fellowship. This work was supported by grants from the NIH and the European Research Council (ERC) to E. S. and student research grants from the Kahn Center for Systems Biology to S.W.G. and the Azrieli Center for Systems Biology to S.W.G. and S.E.K. Data are deposited in Gene Expression Omnibus (GEO) under accession number GSE74277. Author contributions: S.W.G. concieved the project and devised the experiments, designed the synthetic library, performed experiments, analyzed the data and wrote the manuscript; S.E.K. designed the synthetic library and performed experiments; R.N. performed experiments and provided critical comments on the manuscript; A.A.G performed analyses; N.S.G. performed experiments; Z.Y. contributed to the design and analyses; A.W. contributed to the experimental setting; and E. S. conceived the project, supervised the analyses, and wrote the manuscript.
PY - 2016/1/15
Y1 - 2016/1/15
N2 - To investigate gene specificity at the level of translation in both the human genome and viruses, we devised a high-throughput bicistronic assay to quantify cap-independent translation.We uncovered thousands of novel cap-independent translation sequences, and we provide insights on the landscape of translational regulation in both humans and viruses.We find extensive translational elements in the 3? untranslated region of human transcripts and the polyprotein region of uncapped RNA viruses. Through the characterization of regulatory elements underlying cap-independent translation activity, we identify potential mechanisms of secondary structure, short sequence motif, and base pairing with the 18S ribosomal RNA (rRNA). Furthermore, we systematically map the 18S rRNA regions for which reverse complementarity enhances translation. Thus, we make available insights into the mechanisms of translational control in humans and viruses.
AB - To investigate gene specificity at the level of translation in both the human genome and viruses, we devised a high-throughput bicistronic assay to quantify cap-independent translation.We uncovered thousands of novel cap-independent translation sequences, and we provide insights on the landscape of translational regulation in both humans and viruses.We find extensive translational elements in the 3? untranslated region of human transcripts and the polyprotein region of uncapped RNA viruses. Through the characterization of regulatory elements underlying cap-independent translation activity, we identify potential mechanisms of secondary structure, short sequence motif, and base pairing with the 18S ribosomal RNA (rRNA). Furthermore, we systematically map the 18S rRNA regions for which reverse complementarity enhances translation. Thus, we make available insights into the mechanisms of translational control in humans and viruses.
UR - http://www.scopus.com/inward/record.url?scp=84958052052&partnerID=8YFLogxK
U2 - 10.1126/science.aad4939
DO - 10.1126/science.aad4939
M3 - مقالة
C2 - 26816383
SN - 0036-8075
VL - 351
JO - Science
JF - Science
IS - 6270
M1 - aad4939
ER -