Exonuclease-mediated degradation of nascent RNA silences genes linked to severe malaria

Research output: Contribution to journal › Journal article › Research › peer-review

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Exonuclease-mediated degradation of nascent RNA silences genes linked to severe malaria. / Zhang, Qingfeng; Siegel, T Nicolai; Martins, Rafael M; Wang, Fei; Cao, Jun; Gao, Qi; Cheng, Xiu; Jiang, Lubin; Hon, Chung-Chau; Scheidig-Benatar, Christine; Sakamoto, Hiroshi; Turner, Louise; Jensen, Anja Tatiana Ramstedt; Claes, Aurelie; Guizetti, Julien; Malmquist, Nicholas A; Scherf, Artur.

In: Nature, Vol. 531, 2014, p. 431-435.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Zhang, Q, Siegel, TN, Martins, RM, Wang, F, Cao, J, Gao, Q, Cheng, X, Jiang, L, Hon, C-C, Scheidig-Benatar, C, Sakamoto, H, Turner, L, Jensen, ATR, Claes, A, Guizetti, J, Malmquist, NA & Scherf, A 2014, 'Exonuclease-mediated degradation of nascent RNA silences genes linked to severe malaria', Nature, vol. 531, pp. 431-435. https://doi.org/10.1038/nature13468

APA

Zhang, Q., Siegel, T. N., Martins, R. M., Wang, F., Cao, J., Gao, Q., Cheng, X., Jiang, L., Hon, C-C., Scheidig-Benatar, C., Sakamoto, H., Turner, L., Jensen, A. T. R., Claes, A., Guizetti, J., Malmquist, N. A., & Scherf, A. (2014). Exonuclease-mediated degradation of nascent RNA silences genes linked to severe malaria. Nature, 531, 431-435. https://doi.org/10.1038/nature13468

Vancouver

Zhang Q, Siegel TN, Martins RM, Wang F, Cao J, Gao Q et al. Exonuclease-mediated degradation of nascent RNA silences genes linked to severe malaria. Nature. 2014;531:431-435. https://doi.org/10.1038/nature13468

Author

Zhang, Qingfeng ; Siegel, T Nicolai ; Martins, Rafael M ; Wang, Fei ; Cao, Jun ; Gao, Qi ; Cheng, Xiu ; Jiang, Lubin ; Hon, Chung-Chau ; Scheidig-Benatar, Christine ; Sakamoto, Hiroshi ; Turner, Louise ; Jensen, Anja Tatiana Ramstedt ; Claes, Aurelie ; Guizetti, Julien ; Malmquist, Nicholas A ; Scherf, Artur. / Exonuclease-mediated degradation of nascent RNA silences genes linked to severe malaria. In: Nature. 2014 ; Vol. 531. pp. 431-435.

Bibtex

@article{13af7e97eabd4fb5ab03b6090348d39f,
title = "Exonuclease-mediated degradation of nascent RNA silences genes linked to severe malaria",
abstract = "Antigenic variation of the Plasmodium falciparum multicopy var gene family enables parasite evasion of immune destruction by host antibodies. Expression of a particular var subgroup, termed upsA, is linked to the obstruction of blood vessels in the brain and to the pathogenesis of human cerebral malaria. The mechanism determining upsA activation remains unknown. Here we show that an entirely new type of gene silencing mechanism involving an exonuclease-mediated degradation of nascent RNA controls the silencing of genes linked to severe malaria. We identify a novel chromatin-associated exoribonuclease, termed PfRNase II, that controls the silencing of upsA var genes by marking their transcription start site and intron-promoter regions leading to short-lived cryptic RNA. Parasites carrying a deficient PfRNase II gene produce full-length upsA var transcripts and intron-derived antisense long non-coding RNA. The presence of stable upsA var transcripts overcomes monoallelic expression, resulting in the simultaneous expression of both upsA and upsC type PfEMP1 proteins on the surface of individual infected red blood cells. In addition, we observe an inverse relationship between transcript levels of PfRNase II and upsA-type var genes in parasites from severe malaria patients, implying a crucial role of PfRNase II in severe malaria. Our results uncover a previously unknown type of post-transcriptional gene silencing mechanism in malaria parasites with repercussions for other organisms. Additionally, the identification of RNase II as a parasite protein controlling the expression of virulence genes involved in pathogenesis in patients with severe malaria may provide new strategies for reducing malaria mortality.",
author = "Qingfeng Zhang and Siegel, {T Nicolai} and Martins, {Rafael M} and Fei Wang and Jun Cao and Qi Gao and Xiu Cheng and Lubin Jiang and Chung-Chau Hon and Christine Scheidig-Benatar and Hiroshi Sakamoto and Louise Turner and Jensen, {Anja Tatiana Ramstedt} and Aurelie Claes and Julien Guizetti and Malmquist, {Nicholas A} and Artur Scherf",
year = "2014",
doi = "10.1038/nature13468",
language = "English",
volume = "531",
pages = "431--435",
journal = "Nature",
issn = "0028-0836",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Exonuclease-mediated degradation of nascent RNA silences genes linked to severe malaria

AU - Zhang, Qingfeng

AU - Siegel, T Nicolai

AU - Martins, Rafael M

AU - Wang, Fei

AU - Cao, Jun

AU - Gao, Qi

AU - Cheng, Xiu

AU - Jiang, Lubin

AU - Hon, Chung-Chau

AU - Scheidig-Benatar, Christine

AU - Sakamoto, Hiroshi

AU - Turner, Louise

AU - Jensen, Anja Tatiana Ramstedt

AU - Claes, Aurelie

AU - Guizetti, Julien

AU - Malmquist, Nicholas A

AU - Scherf, Artur

PY - 2014

Y1 - 2014

N2 - Antigenic variation of the Plasmodium falciparum multicopy var gene family enables parasite evasion of immune destruction by host antibodies. Expression of a particular var subgroup, termed upsA, is linked to the obstruction of blood vessels in the brain and to the pathogenesis of human cerebral malaria. The mechanism determining upsA activation remains unknown. Here we show that an entirely new type of gene silencing mechanism involving an exonuclease-mediated degradation of nascent RNA controls the silencing of genes linked to severe malaria. We identify a novel chromatin-associated exoribonuclease, termed PfRNase II, that controls the silencing of upsA var genes by marking their transcription start site and intron-promoter regions leading to short-lived cryptic RNA. Parasites carrying a deficient PfRNase II gene produce full-length upsA var transcripts and intron-derived antisense long non-coding RNA. The presence of stable upsA var transcripts overcomes monoallelic expression, resulting in the simultaneous expression of both upsA and upsC type PfEMP1 proteins on the surface of individual infected red blood cells. In addition, we observe an inverse relationship between transcript levels of PfRNase II and upsA-type var genes in parasites from severe malaria patients, implying a crucial role of PfRNase II in severe malaria. Our results uncover a previously unknown type of post-transcriptional gene silencing mechanism in malaria parasites with repercussions for other organisms. Additionally, the identification of RNase II as a parasite protein controlling the expression of virulence genes involved in pathogenesis in patients with severe malaria may provide new strategies for reducing malaria mortality.

AB - Antigenic variation of the Plasmodium falciparum multicopy var gene family enables parasite evasion of immune destruction by host antibodies. Expression of a particular var subgroup, termed upsA, is linked to the obstruction of blood vessels in the brain and to the pathogenesis of human cerebral malaria. The mechanism determining upsA activation remains unknown. Here we show that an entirely new type of gene silencing mechanism involving an exonuclease-mediated degradation of nascent RNA controls the silencing of genes linked to severe malaria. We identify a novel chromatin-associated exoribonuclease, termed PfRNase II, that controls the silencing of upsA var genes by marking their transcription start site and intron-promoter regions leading to short-lived cryptic RNA. Parasites carrying a deficient PfRNase II gene produce full-length upsA var transcripts and intron-derived antisense long non-coding RNA. The presence of stable upsA var transcripts overcomes monoallelic expression, resulting in the simultaneous expression of both upsA and upsC type PfEMP1 proteins on the surface of individual infected red blood cells. In addition, we observe an inverse relationship between transcript levels of PfRNase II and upsA-type var genes in parasites from severe malaria patients, implying a crucial role of PfRNase II in severe malaria. Our results uncover a previously unknown type of post-transcriptional gene silencing mechanism in malaria parasites with repercussions for other organisms. Additionally, the identification of RNase II as a parasite protein controlling the expression of virulence genes involved in pathogenesis in patients with severe malaria may provide new strategies for reducing malaria mortality.

U2 - 10.1038/nature13468

DO - 10.1038/nature13468

M3 - Journal article

C2 - 25043062

VL - 531

SP - 431

EP - 435

JO - Nature

JF - Nature

SN - 0028-0836

ER -

ID: 120329646