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MS-Based Approaches for Nucleic Acid Structural Determination

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Nucleic Acids in the Gas Phase

Part of the book series: Physical Chemistry in Action ((PCIA))

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Abstract

The vast majority of the human genome consists of sequences that do not code for proteins. Understanding their function must rely on approaches that are capable of providing more than mere sequence information. Alone or in combination with other techniques, mass spectrometry (MS) can provide an excellent platform for investigating non-coding nucleic acids (NA) at many different levels. This chapter reviews MS-based approaches developed to pursue the structural elucidation of species that are not readily amenable to the classic high-resolution techniques. Indeed, MS has recently found increasing applications as a detection platform for chemical probes used to interrogate NA structure in solution. These developments have been riding on the concomitant advances of computational approaches, which are rapidly closing the resolution gap with NMR and crystallography by taking full advantage of the sparse constraints afforded by alternative techniques. Further, the hierarchic nature of NA structure, which is characterized by the three-dimensional organization of discrete structural elements, lends itself well to the investigation by techniques that are capable of revealing the position of structure-defining interactions. For this reason, novel strategies are being developed to study secondary, tertiary, and quaternary interactions in the gas phase, which may retain memory of the solution architecture. The popularization of ion mobility spectrometry (IMS) has opened new avenues for investigating the overall topology of non-coding elements, which promise to contribute significantly to the elucidation of progressively larger NA systems.

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Abbreviations

A:

Adenine nucleotide

BDG:

4,4′-Bihenyl-diglyoxal

BKT:

Bikethoxal

C:

Cytosine nucleotide

CASP:

Critical assessment of protein structure prediction

CCS:

Collisional cross section

CID:

Collision-induced dissociation

CMCT:

1-Cyclohexyl-3-(2-morpholinoethyl)-carbodiimide metho-p-toluene sulfonate

CPT:

Cisplatin

DMS:

Dimethylsulfate

DNA:

Deoxyribonucleic acid

ECD:

Electron capture dissociation

EDD:

Electron detachment dissociation

EDTA:

Ethylenediaminetetraacetic acid

ESI:

Electrospray ionization

FIV:

Feline immunodeficiency virus

G:

Guanine nucleotide

GUI:

Graphic user interface

HDX:

Hydrogen–deuterium exchange

HIV-1:

Immunodeficiency virus type 1

IMS:

Ion mobility spectrometry

IRMPD:

Infrared multiphoton dissociation

KT:

Kethoxal, β-ethoxy-α-ketobutyraldehyde

MALDI:

Matrix-assisted laser desorption ionization

mRNA:

Messenger ribonucleic acid

MS:

Mass spectrometry

MS/MS:

Tandem mass spectrometry

MS3D:

Mass spectrometry three-dimensional

NA:

Nucleic acids

NB:

Neomycin B

NC:

HIV-1 nucleocapsid protein

NM:

Nitrogen mustard

NMIA:

N-methylisatoic anhydride

NMR:

Nuclear magnetic resonance

PCR:

Polymerase chain reaction

PDG:

1,4-Phenyl-diglyoxal

PPT:

Polypurine tract

RMSD:

Root mean square deviation

RNA:

Ribonucleic acid

SAXS:

Small-angle X-ray scattering

SHAMS:

2′-Hydroxyl acylation by mass spectrometry

SHAPE:

2′-Hydroxyl acylation by primer extension

SL1 though 4:

HIV-1 stemloop 1 through 4

T:

Thymine nucleotide

U:

Uracil nucleotide

UV:

Ultraviolet

WC:

Watson–Crick

Ψ-RNA:

HIV-1 packaging signal

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Acknowledgments

Financial support was provided by The RNA Institute through a Pilot Research Program grant.

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  1. The RNA Institute, University at Albany (SUNY), Life Sciences Research Building room 1109, 1200 Washington Avenue, Albany, NY, 12222, USA

    Daniele Fabris

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  1. Université de Bordeaux, Institut Européen de Chimie et Biologie, Pessac, France

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Fabris, D. (2014). MS-Based Approaches for Nucleic Acid Structural Determination. In: Gabelica, V. (eds) Nucleic Acids in the Gas Phase. Physical Chemistry in Action. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-54842-0_10

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