Human DNA tumor viruses generate alternative reading frame proteins through repeat sequence recoding

Hyun Jin Kwun, Tuna Toptan, Suzane Ramos Da Silva, John F. Atkins, Patrick S. Moore, Yuan Chang

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are human DNA tumor viruses that express nuclear antigens [latency-associated nuclear antigen 1 (LANA1) and Epstein-Barr nuclear antigen 1 (EBNA1)] necessary to maintain and replicate the viral genome. We report here that both LANA1 and EBNA1 undergo highly efficient +1/-2 programmed ribosomal frameshifting to generate previously undescribed alternative reading frame (ARF) proteins in their repeat regions. EBNA1ARF encodes a KSHV LANA-like glutamine- and glutamic acid-rich protein, whereas KSHV LANA1ARFencodes a serine/arginine-like protein. Repeat sequence recoding has not been described previously for human DNA viruses. Programmed frameshifting (recoding) to generate multiple proteins from one RNA sequence can increase the coding capacity of a virus, without incurring a selective penalty against increased capsid size. The presence of similar repeat sequences in cellular genes, such as huntingtin, suggests that a comparison of repeat recoding in virus and human systems may provide functional and mechanistic insights for both systems.

Original languageEnglish (US)
Pages (from-to)E4342-E4349
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number41
DOIs
StatePublished - Oct 14 2014

Fingerprint

DNA Tumor Viruses
Reading Frames
Human Herpesvirus 8
Nuclear Antigens
Proteins
Ribosomal Frameshifting
Viruses
DNA Viruses
Viral Genome
Capsid
Glutamine
Human Herpesvirus 4
Serine
Arginine
Glutamic Acid
Genes

All Science Journal Classification (ASJC) codes

  • General

Cite this

Kwun, Hyun Jin ; Toptan, Tuna ; Da Silva, Suzane Ramos ; Atkins, John F. ; Moore, Patrick S. ; Chang, Yuan. / Human DNA tumor viruses generate alternative reading frame proteins through repeat sequence recoding. In: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; Vol. 111, No. 41. pp. E4342-E4349.
@article{886fc44d96f7420eacf8dc4d4bd75043,
title = "Human DNA tumor viruses generate alternative reading frame proteins through repeat sequence recoding",
abstract = "Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are human DNA tumor viruses that express nuclear antigens [latency-associated nuclear antigen 1 (LANA1) and Epstein-Barr nuclear antigen 1 (EBNA1)] necessary to maintain and replicate the viral genome. We report here that both LANA1 and EBNA1 undergo highly efficient +1/-2 programmed ribosomal frameshifting to generate previously undescribed alternative reading frame (ARF) proteins in their repeat regions. EBNA1ARF encodes a KSHV LANA-like glutamine- and glutamic acid-rich protein, whereas KSHV LANA1ARFencodes a serine/arginine-like protein. Repeat sequence recoding has not been described previously for human DNA viruses. Programmed frameshifting (recoding) to generate multiple proteins from one RNA sequence can increase the coding capacity of a virus, without incurring a selective penalty against increased capsid size. The presence of similar repeat sequences in cellular genes, such as huntingtin, suggests that a comparison of repeat recoding in virus and human systems may provide functional and mechanistic insights for both systems.",
author = "Kwun, {Hyun Jin} and Tuna Toptan and {Da Silva}, {Suzane Ramos} and Atkins, {John F.} and Moore, {Patrick S.} and Yuan Chang",
year = "2014",
month = "10",
day = "14",
doi = "10.1073/pnas.1416122111",
language = "English (US)",
volume = "111",
pages = "E4342--E4349",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "41",

}

Human DNA tumor viruses generate alternative reading frame proteins through repeat sequence recoding. / Kwun, Hyun Jin; Toptan, Tuna; Da Silva, Suzane Ramos; Atkins, John F.; Moore, Patrick S.; Chang, Yuan.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 41, 14.10.2014, p. E4342-E4349.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Human DNA tumor viruses generate alternative reading frame proteins through repeat sequence recoding

AU - Kwun, Hyun Jin

AU - Toptan, Tuna

AU - Da Silva, Suzane Ramos

AU - Atkins, John F.

AU - Moore, Patrick S.

AU - Chang, Yuan

PY - 2014/10/14

Y1 - 2014/10/14

N2 - Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are human DNA tumor viruses that express nuclear antigens [latency-associated nuclear antigen 1 (LANA1) and Epstein-Barr nuclear antigen 1 (EBNA1)] necessary to maintain and replicate the viral genome. We report here that both LANA1 and EBNA1 undergo highly efficient +1/-2 programmed ribosomal frameshifting to generate previously undescribed alternative reading frame (ARF) proteins in their repeat regions. EBNA1ARF encodes a KSHV LANA-like glutamine- and glutamic acid-rich protein, whereas KSHV LANA1ARFencodes a serine/arginine-like protein. Repeat sequence recoding has not been described previously for human DNA viruses. Programmed frameshifting (recoding) to generate multiple proteins from one RNA sequence can increase the coding capacity of a virus, without incurring a selective penalty against increased capsid size. The presence of similar repeat sequences in cellular genes, such as huntingtin, suggests that a comparison of repeat recoding in virus and human systems may provide functional and mechanistic insights for both systems.

AB - Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are human DNA tumor viruses that express nuclear antigens [latency-associated nuclear antigen 1 (LANA1) and Epstein-Barr nuclear antigen 1 (EBNA1)] necessary to maintain and replicate the viral genome. We report here that both LANA1 and EBNA1 undergo highly efficient +1/-2 programmed ribosomal frameshifting to generate previously undescribed alternative reading frame (ARF) proteins in their repeat regions. EBNA1ARF encodes a KSHV LANA-like glutamine- and glutamic acid-rich protein, whereas KSHV LANA1ARFencodes a serine/arginine-like protein. Repeat sequence recoding has not been described previously for human DNA viruses. Programmed frameshifting (recoding) to generate multiple proteins from one RNA sequence can increase the coding capacity of a virus, without incurring a selective penalty against increased capsid size. The presence of similar repeat sequences in cellular genes, such as huntingtin, suggests that a comparison of repeat recoding in virus and human systems may provide functional and mechanistic insights for both systems.

UR - http://www.scopus.com/inward/record.url?scp=84907895360&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907895360&partnerID=8YFLogxK

U2 - 10.1073/pnas.1416122111

DO - 10.1073/pnas.1416122111

M3 - Article

C2 - 25271323

AN - SCOPUS:84907895360

VL - 111

SP - E4342-E4349

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 41

ER -