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Nuclear Export of mRNAs with Disease Pathogenesis and Therapeutic Implications

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Messenger RNA Therapeutics

Part of the book series: RNA Technologies ((RNATECHN,volume 13))

Abstract

In eukaryotes, RNA polymerase II genes are transcribed to mRNAs, processed in the nucleus, and then exported to the cytoplasm through the nuclear pore complex for translation to proteins. Thus, eukaryotic gene expression is regulated at multiple steps via coordinated actions of a large number of proteins in different cellular compartments. In this chapter, we describe how gene expression is controlled at the level of mRNA export from nucleus to the cytoplasm with implications for disease pathogenesis and therapeutic development.

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Abbreviations

4E-SE:

eIF4E sensitivity element

AD:

Alzheimer’s disease

AML-1:

Acute myeloid leukemia

AREX:

Alternative mRNA export

ARE:

AU-rich elements

ALS:

Amyotrophic lateral sclerosis

ASOs:

Antisense oligonucleotides

CBC:

Cap-binding complex

CETN2/3:

Centrin2/3

CIP29:

29 kDa cytokine-induced protein

CRM1:

Chromosome region maintenance 1

DBP5:

DEAD-box protein 5

DSS1:

Deletion of Suv3 suppressor 1

DUB:

De-ubiquitination

ENY2:

Enhancer of yellow 2

FACT:

Facilitates chromatin transcription

FDA:

Food and drug administration

FTD:

Frontotemporal dementia

GANP:

Germinal –center-associated nuclear protein

GLE1:

GLFG (glycine–leucine-phenylalanine–glycine) lethal

HD:

Huntington’s disease

HECT:

Homologous to E6AP carboxyl terminus

HuR:

Human antigen R

IP6:

Inositol hexaphosphate

iPSC:

Induced pluripotent stem cells

LAAHD:

Lethal arthrogryposis with anterior horn cell disease

LEF-1:

Lymphoid enhancer-binding factor 1

LCCS1:

Lethal congenital contracture syndrome 1

LRR:

Leucine-rich repeat

LRPPRC:

Leucine-rich pentatricopeptide repeat-containing

MAP1:

Microtubule-associated protein 1

MBLN1:

Muscleblind-like 1

MDS:

Myelodysplastic syndromes

MDM2:

Mouse double minute 2 homolog

mRNP:

Messenger ribonucleoprotein

NEDD8:

Neural precursor cell expressed developmentally down-regulated 8

NES:

Nuclear export signal

NPC:

Nuclear pore complex

NTF2L:

Nuclear transport factor 2-like

Nups:

Nucleoporins

NXF1:

Nuclear RNA export factor 1

NXT1:

Nuclear transport factor 2-like export factor 1

PCID2:

PCI domain containing 2

Ran:

Ras-related nuclear protein

RanBP3:

Ran-binding protein 3

Ran-GAP:

Ran GTPase activating protein

RBD:

RNA-binding domain

RING:

Really interesting new gene

RRM:

RNA recognition motif

SAGA:

Spt-Ada-Gcn5-acetyltransferase

SCF:

Skp1-cullin1-F-box

SCA7:

Spinocerebellar ataxia type 7

SGF73:

SAGA-associated factor 73 kDa

SINE:

Selective inhibitors of nuclear export

TDP43:

TAR DNA-binding protein 43

THOC1:

THO complex 1

TREX:

Transcription export

UAP56:

U2AF65-associated protein 56

UBA:

Ubiquitin-associated

UBM:

UAP56-binding motif

UIF:

UAP56 interacting factor

UPS:

Ubiquitin proteasome system

USP2:

Ubiquitin-specific protease 2

UTR:

Untranslated region

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Acknowledgements

The work in the Bhaumik laboratory was supported by National Institutes of Health grants (1R15GM088798-01, 1R15GM088798-02, and 1R15GM088798-03), a National Scientist Development Grant (0635008N) from American Heart Association, Grants-in-aid from the American Heart Association (10GRNT4300059 and 15GRNT25700298), a Research Scholar Grant (06-52) from American Cancer Society, a Mallinckrodt Foundation Award, and multiple internal grants from Southern Illinois University. Shalini Guha is supported by the doctoral fellowship of Southern Illinois University, Carbondale. We apologize to the authors whose work could not be cited owing to space limitations.

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  1. Department of Biochemistry and Molecular Biology, Southern Illinois University School of Medicine, Carbondale, IL-62901, USA

    Shalini Guha, Priyanka Barman, Aruniti Manawa & Sukesh R. Bhaumik

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  1. Shalini Guha
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Correspondence to Sukesh R. Bhaumik .

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  1. NanoBioMedical Center, Adam Mickiewicz University, Poznań, Poland

    Stefan Jurga

  2. NanoBioMedical Center, Adam Mickiewicz University, Poznań, Poland

    Jan Barciszewski

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Guha, S., Barman, P., Manawa, A., Bhaumik, S.R. (2022). Nuclear Export of mRNAs with Disease Pathogenesis and Therapeutic Implications. In: Jurga, S., Barciszewski, J. (eds) Messenger RNA Therapeutics. RNA Technologies, vol 13. Springer, Cham. https://doi.org/10.1007/978-3-031-08415-7_17

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