Structure and Function of RNase AS, a Polyadenylate-Specific Exoribonuclease Affecting Mycobacterial Virulence In Vivo

Maria Romano; Robert van de Weerd; Femke C. C. Brouwer; Giovanni N. Roviello; Ruben Lacroix; Marion Sparrius; Gunny van den Brink-van Stempvoort; Ben J. Appelmelk; Jeroen J. Geurtsen; Rita Berisio; Femke van Rhijn

doi:10.1016/j.str.2014.01.014

Structure and Function of RNase AS, a Polyadenylate-Specific Exoribonuclease Affecting Mycobacterial Virulence In Vivo

Maria Romano, Robert van de Weerd, Femke C. C. Brouwer, Giovanni N. Roviello, Ruben Lacroix, Marion Sparrius, Gunny van den Brink-van Stempvoort, Ben J. Appelmelk^*, Jeroen J. Geurtsen, Rita Berisio, Femke van Rhijn

^*Corresponding author for this work

Nephrology

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

Abstract

The cell-envelope of Mycobacterium tuberculosis plays a key role in bacterial virulence and antibiotic resistance. Little is known about the molecular mechanisms of regulation of cell-envelope formation. Here, we elucidate functional and structural properties of RNase AS, which modulates M. tuberculosis cell-envelope properties and strongly impacts bacterial virulence in vivo. The structure of RNase AS reveals a resemblance to RNase T from Escherichia coli, an RNase of the DEDD family involved in RNA maturation. We show that RNase AS acts as a 3 '-5 '-exoribonuclease that specifically hydrolyzes adenylate-containing RNA sequences. Also, crystal structures of complexes with AMP and UMP reveal the structural basis for the observed enzyme specificity. Notably, RNase AS shows a mechanism of substrate recruitment, based on the recognition of the hydrogen bond donor NH2 group of adenine. Our work opens a field for the design of drugs able to reduce bacterial virulence in vivo.

Original language	English
Pages (from-to)	719-730
Number of pages	12
Journal	Structure
Volume	22
Issue number	5
DOIs	https://doi.org/10.1016/j.str.2014.01.014
Publication status	Published - 6 May 2014

Keywords

CRYSTAL-STRUCTURE
ESCHERICHIA-COLI
CELL-WALL
TUBERCULOSIS
PROTEIN
MODEL
LIPOARABINOMANNAN
BIOSYNTHESIS
BINDING
MANNOSYLTRANSFERASE

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10.1016/j.str.2014.01.014

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Romano, M., van de Weerd, R., Brouwer, F. C. C., Roviello, G. N., Lacroix, R., Sparrius, M., van den Brink-van Stempvoort, G., Appelmelk, B. J., Geurtsen, J. J., Berisio, R., & van Rhijn, F. (2014). Structure and Function of RNase AS, a Polyadenylate-Specific Exoribonuclease Affecting Mycobacterial Virulence In Vivo. Structure, 22(5), 719-730. https://doi.org/10.1016/j.str.2014.01.014

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title = "Structure and Function of RNase AS, a Polyadenylate-Specific Exoribonuclease Affecting Mycobacterial Virulence In Vivo",

abstract = "The cell-envelope of Mycobacterium tuberculosis plays a key role in bacterial virulence and antibiotic resistance. Little is known about the molecular mechanisms of regulation of cell-envelope formation. Here, we elucidate functional and structural properties of RNase AS, which modulates M. tuberculosis cell-envelope properties and strongly impacts bacterial virulence in vivo. The structure of RNase AS reveals a resemblance to RNase T from Escherichia coli, an RNase of the DEDD family involved in RNA maturation. We show that RNase AS acts as a 3 '-5 '-exoribonuclease that specifically hydrolyzes adenylate-containing RNA sequences. Also, crystal structures of complexes with AMP and UMP reveal the structural basis for the observed enzyme specificity. Notably, RNase AS shows a mechanism of substrate recruitment, based on the recognition of the hydrogen bond donor NH2 group of adenine. Our work opens a field for the design of drugs able to reduce bacterial virulence in vivo.",

keywords = "CRYSTAL-STRUCTURE, ESCHERICHIA-COLI, CELL-WALL, TUBERCULOSIS, PROTEIN, MODEL, LIPOARABINOMANNAN, BIOSYNTHESIS, BINDING, MANNOSYLTRANSFERASE",

author = "Maria Romano and {van de Weerd}, Robert and Brouwer, {Femke C. C.} and Roviello, {Giovanni N.} and Ruben Lacroix and Marion Sparrius and {van den Brink-van Stempvoort}, Gunny and Appelmelk, {Ben J.} and Geurtsen, {Jeroen J.} and Rita Berisio and {van Rhijn}, Femke",

year = "2014",

month = may,

day = "6",

doi = "10.1016/j.str.2014.01.014",

language = "English",

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pages = "719--730",

journal = "Structure",

issn = "0969-2126",

publisher = "Cell Press",

number = "5",

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Romano, M, van de Weerd, R, Brouwer, FCC, Roviello, GN, Lacroix, R, Sparrius, M, van den Brink-van Stempvoort, G, Appelmelk, BJ, Geurtsen, JJ, Berisio, R & van Rhijn, F 2014, 'Structure and Function of RNase AS, a Polyadenylate-Specific Exoribonuclease Affecting Mycobacterial Virulence In Vivo', Structure, vol. 22, no. 5, pp. 719-730. https://doi.org/10.1016/j.str.2014.01.014

TY - JOUR

T1 - Structure and Function of RNase AS, a Polyadenylate-Specific Exoribonuclease Affecting Mycobacterial Virulence In Vivo

AU - Romano, Maria

AU - van de Weerd, Robert

AU - Brouwer, Femke C. C.

AU - Roviello, Giovanni N.

AU - Lacroix, Ruben

AU - Sparrius, Marion

AU - van den Brink-van Stempvoort, Gunny

AU - Appelmelk, Ben J.

AU - Geurtsen, Jeroen J.

AU - Berisio, Rita

AU - van Rhijn, Femke

PY - 2014/5/6

Y1 - 2014/5/6

N2 - The cell-envelope of Mycobacterium tuberculosis plays a key role in bacterial virulence and antibiotic resistance. Little is known about the molecular mechanisms of regulation of cell-envelope formation. Here, we elucidate functional and structural properties of RNase AS, which modulates M. tuberculosis cell-envelope properties and strongly impacts bacterial virulence in vivo. The structure of RNase AS reveals a resemblance to RNase T from Escherichia coli, an RNase of the DEDD family involved in RNA maturation. We show that RNase AS acts as a 3 '-5 '-exoribonuclease that specifically hydrolyzes adenylate-containing RNA sequences. Also, crystal structures of complexes with AMP and UMP reveal the structural basis for the observed enzyme specificity. Notably, RNase AS shows a mechanism of substrate recruitment, based on the recognition of the hydrogen bond donor NH2 group of adenine. Our work opens a field for the design of drugs able to reduce bacterial virulence in vivo.

AB - The cell-envelope of Mycobacterium tuberculosis plays a key role in bacterial virulence and antibiotic resistance. Little is known about the molecular mechanisms of regulation of cell-envelope formation. Here, we elucidate functional and structural properties of RNase AS, which modulates M. tuberculosis cell-envelope properties and strongly impacts bacterial virulence in vivo. The structure of RNase AS reveals a resemblance to RNase T from Escherichia coli, an RNase of the DEDD family involved in RNA maturation. We show that RNase AS acts as a 3 '-5 '-exoribonuclease that specifically hydrolyzes adenylate-containing RNA sequences. Also, crystal structures of complexes with AMP and UMP reveal the structural basis for the observed enzyme specificity. Notably, RNase AS shows a mechanism of substrate recruitment, based on the recognition of the hydrogen bond donor NH2 group of adenine. Our work opens a field for the design of drugs able to reduce bacterial virulence in vivo.

KW - CRYSTAL-STRUCTURE

KW - ESCHERICHIA-COLI

KW - CELL-WALL

KW - TUBERCULOSIS

KW - PROTEIN

KW - MODEL

KW - LIPOARABINOMANNAN

KW - BIOSYNTHESIS

KW - BINDING

KW - MANNOSYLTRANSFERASE

U2 - 10.1016/j.str.2014.01.014

DO - 10.1016/j.str.2014.01.014

M3 - Article

C2 - 24704253

SN - 0969-2126

VL - 22

SP - 719

EP - 730

JO - Structure

JF - Structure

IS - 5

ER -

Structure and Function of RNase AS, a Polyadenylate-Specific Exoribonuclease Affecting Mycobacterial Virulence In Vivo

Abstract

Keywords

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