t6A and ms2t6A Modified Nucleosides in Serum and Urine as Strong Candidate Biomarkers of COVID-19 Infection and Severity

Yu Nagayoshi; Kayo Nishiguchi; Ryosuke Yamamura; Takeshi Chujo; Hiroyuki Oshiumi; Hiroko Nagata; Hitomi Kaneko; Keiichi Yamamoto; Hirotomo Nakata; Korin Sakakida; Akihiro Kunisawa; Masataka Adachi; Yutaka Kakizoe; Takanori Mizobe; Jun Ichi Kuratsu; Shinya Shimada; Yasushi Nakamori; Masao Matsuoka; Masashi Mukoyama; Fan Yan Wei; Kazuhito Tomizawa

doi:10.3390/biom12091233

t⁶A and ms²t⁶A Modified Nucleosides in Serum and Urine as Strong Candidate Biomarkers of COVID-19 Infection and Severity

Yu Nagayoshi, Kayo Nishiguchi, Ryosuke Yamamura, Takeshi Chujo, Hiroyuki Oshiumi, Hiroko Nagata, Hitomi Kaneko, Keiichi Yamamoto, Hirotomo Nakata, Korin Sakakida, Akihiro Kunisawa, Masataka Adachi, Yutaka Kakizoe, Takanori Mizobe, Jun Ichi Kuratsu, Shinya Shimada, Yasushi Nakamori, Masao Matsuoka, Masashi Mukoyama, Fan Yan WeiKazuhito Tomizawa

Division of Aging Science

Research output: Contribution to journal › Article › peer-review

Abstract

SARS-CoV-2 infection alters cellular RNA content. Cellular RNAs are chemically modified and eventually degraded, depositing modified nucleosides into extracellular fluids such as serum and urine. Here we searched for COVID-19-specific changes in modified nucleoside levels contained in serum and urine of 308 COVID-19 patients using liquid chromatography-mass spectrometry (LC-MS). We found that two modified nucleosides, N⁶-threonylcarbamoyladenosine (t⁶A) and 2-methylthio-N⁶-threonylcarbamoyladenosine (ms²t⁶A), were elevated in serum and urine of COVID-19 patients. Moreover, these levels were associated with symptom severity and decreased upon recovery from COVID-19. In addition, the elevation of similarly modified nucleosides was observed regardless of COVID-19 variants. These findings illuminate specific modified RNA nucleosides in the extracellular fluids as biomarkers for COVID-19 infection and severity.

Original language	English
Article number	1233
Journal	Biomolecules
Volume	12
Issue number	9
DOIs	https://doi.org/10.3390/biom12091233
Publication status	Published - 2022 Sept

Keywords

COVID-19
LC-MS
modified nucleosides

ASJC Scopus subject areas

Biochemistry
Molecular Biology

Access to Document

10.3390/biom12091233

Cite this

Nagayoshi, Y., Nishiguchi, K., Yamamura, R., Chujo, T., Oshiumi, H., Nagata, H., Kaneko, H., Yamamoto, K., Nakata, H., Sakakida, K., Kunisawa, A., Adachi, M., Kakizoe, Y., Mizobe, T., Kuratsu, J. I., Shimada, S., Nakamori, Y., Matsuoka, M., Mukoyama, M., ... Tomizawa, K. (2022). t⁶A and ms²t⁶A Modified Nucleosides in Serum and Urine as Strong Candidate Biomarkers of COVID-19 Infection and Severity. Biomolecules, 12(9), [1233]. https://doi.org/10.3390/biom12091233

Nagayoshi, Y, Nishiguchi, K, Yamamura, R, Chujo, T, Oshiumi, H, Nagata, H, Kaneko, H, Yamamoto, K, Nakata, H, Sakakida, K, Kunisawa, A, Adachi, M, Kakizoe, Y, Mizobe, T, Kuratsu, JI, Shimada, S, Nakamori, Y, Matsuoka, M, Mukoyama, M, Wei, FY & Tomizawa, K 2022, 't⁶A and ms²t⁶A Modified Nucleosides in Serum and Urine as Strong Candidate Biomarkers of COVID-19 Infection and Severity', Biomolecules, vol. 12, no. 9, 1233. https://doi.org/10.3390/biom12091233

@article{26c13c968b174072839fa475e8badde9,

title = "t6A and ms2t6A Modified Nucleosides in Serum and Urine as Strong Candidate Biomarkers of COVID-19 Infection and Severity",

abstract = "SARS-CoV-2 infection alters cellular RNA content. Cellular RNAs are chemically modified and eventually degraded, depositing modified nucleosides into extracellular fluids such as serum and urine. Here we searched for COVID-19-specific changes in modified nucleoside levels contained in serum and urine of 308 COVID-19 patients using liquid chromatography-mass spectrometry (LC-MS). We found that two modified nucleosides, N6-threonylcarbamoyladenosine (t6A) and 2-methylthio-N6-threonylcarbamoyladenosine (ms2t6A), were elevated in serum and urine of COVID-19 patients. Moreover, these levels were associated with symptom severity and decreased upon recovery from COVID-19. In addition, the elevation of similarly modified nucleosides was observed regardless of COVID-19 variants. These findings illuminate specific modified RNA nucleosides in the extracellular fluids as biomarkers for COVID-19 infection and severity.",

keywords = "COVID-19, LC-MS, modified nucleosides",

author = "Yu Nagayoshi and Kayo Nishiguchi and Ryosuke Yamamura and Takeshi Chujo and Hiroyuki Oshiumi and Hiroko Nagata and Hitomi Kaneko and Keiichi Yamamoto and Hirotomo Nakata and Korin Sakakida and Akihiro Kunisawa and Masataka Adachi and Yutaka Kakizoe and Takanori Mizobe and Kuratsu, {Jun Ichi} and Shinya Shimada and Yasushi Nakamori and Masao Matsuoka and Masashi Mukoyama and Wei, {Fan Yan} and Kazuhito Tomizawa",

note = "Funding Information: This study was supported by grants from the Cooperative Research Project Program of Joint Usage/Research Center at the Institute of Development, Aging and Cancer, Tohoku University, and AMABIE Research Project, Kumamoto University. Funding Information: K.T. was funded by Shimadzu Corporation and AiSTI Science Corporation. Other authors have no competing interest. Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = sep,

doi = "10.3390/biom12091233",

language = "English",

volume = "12",

journal = "Biomolecules",

issn = "2218-273X",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "9",

}

TY - JOUR

T1 - t6A and ms2t6A Modified Nucleosides in Serum and Urine as Strong Candidate Biomarkers of COVID-19 Infection and Severity

AU - Nagayoshi, Yu

AU - Nishiguchi, Kayo

AU - Yamamura, Ryosuke

AU - Chujo, Takeshi

AU - Oshiumi, Hiroyuki

AU - Nagata, Hiroko

AU - Kaneko, Hitomi

AU - Yamamoto, Keiichi

AU - Nakata, Hirotomo

AU - Sakakida, Korin

AU - Kunisawa, Akihiro

AU - Adachi, Masataka

AU - Kakizoe, Yutaka

AU - Mizobe, Takanori

AU - Kuratsu, Jun Ichi

AU - Shimada, Shinya

AU - Nakamori, Yasushi

AU - Matsuoka, Masao

AU - Mukoyama, Masashi

AU - Wei, Fan Yan

AU - Tomizawa, Kazuhito

N1 - Funding Information: This study was supported by grants from the Cooperative Research Project Program of Joint Usage/Research Center at the Institute of Development, Aging and Cancer, Tohoku University, and AMABIE Research Project, Kumamoto University. Funding Information: K.T. was funded by Shimadzu Corporation and AiSTI Science Corporation. Other authors have no competing interest. Publisher Copyright: © 2022 by the authors.

PY - 2022/9

Y1 - 2022/9

N2 - SARS-CoV-2 infection alters cellular RNA content. Cellular RNAs are chemically modified and eventually degraded, depositing modified nucleosides into extracellular fluids such as serum and urine. Here we searched for COVID-19-specific changes in modified nucleoside levels contained in serum and urine of 308 COVID-19 patients using liquid chromatography-mass spectrometry (LC-MS). We found that two modified nucleosides, N6-threonylcarbamoyladenosine (t6A) and 2-methylthio-N6-threonylcarbamoyladenosine (ms2t6A), were elevated in serum and urine of COVID-19 patients. Moreover, these levels were associated with symptom severity and decreased upon recovery from COVID-19. In addition, the elevation of similarly modified nucleosides was observed regardless of COVID-19 variants. These findings illuminate specific modified RNA nucleosides in the extracellular fluids as biomarkers for COVID-19 infection and severity.

AB - SARS-CoV-2 infection alters cellular RNA content. Cellular RNAs are chemically modified and eventually degraded, depositing modified nucleosides into extracellular fluids such as serum and urine. Here we searched for COVID-19-specific changes in modified nucleoside levels contained in serum and urine of 308 COVID-19 patients using liquid chromatography-mass spectrometry (LC-MS). We found that two modified nucleosides, N6-threonylcarbamoyladenosine (t6A) and 2-methylthio-N6-threonylcarbamoyladenosine (ms2t6A), were elevated in serum and urine of COVID-19 patients. Moreover, these levels were associated with symptom severity and decreased upon recovery from COVID-19. In addition, the elevation of similarly modified nucleosides was observed regardless of COVID-19 variants. These findings illuminate specific modified RNA nucleosides in the extracellular fluids as biomarkers for COVID-19 infection and severity.

KW - COVID-19

KW - LC-MS

KW - modified nucleosides

UR - http://www.scopus.com/inward/record.url?scp=85138426443&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85138426443&partnerID=8YFLogxK

U2 - 10.3390/biom12091233

DO - 10.3390/biom12091233

M3 - Article

C2 - 36139072

AN - SCOPUS:85138426443

SN - 2218-273X

VL - 12

JO - Biomolecules

JF - Biomolecules

IS - 9

M1 - 1233

ER -