Crystal structure of the two-RRM domain of hnRNP A1 (UP1) complexed with single-stranded telomeric DNA

Jianzhong Ding, Mariko K. Hayashi, Ying Zhang, Lisa Manche, Adrian R. Krainer, Rui Ming Xu

Research output: Contribution to journalArticle

250 Citations (Scopus)

Abstract

Human hnRNP A1 is a versatile single-stranded nucleic acid-binding protein that functions in various aspects of mRNA maturation and in telomere length regulation. The crystal structure of UP1, the amino-terminal domain of human hnRNP A1 containing two RNA-recognition motifs (RRMs), bound to a 12- nucleotide single-stranded telomeric DNA has been determined at 2.1 Å resolution. The structure of the complex reveals the basis for sequence- specific recognition of the single-stranded overhangs of human telomeres by hnRNP A1. It also provides insights into the basis for high-affinity binding of hnRNP A1 to certain RNA sequences, and for nucleic acid binding and functional synergy between the RRMs. In the crystal structure, a UP1 dimer binds to two strands of DNA, and each strand contacts RRM1 of one monomer and RRM2 of the other. The two DNA strands are antiparallel, and regions of the protein flanking each RRM make important contacts with DNA. The extensive protein-protein interface seen in the crystal structure of the protein-DNA complex and the evolutionary conservation of the interface residues suggest the importance of specific protein-protein interactions for the sequence- specific recognition of single-stranded nucleic acids. Models for regular packaging of telomere 3' overhangs and for juxtaposition of alternative 5' splice sites are proposed.

Original languageEnglish
Pages (from-to)1102-1115
Number of pages14
JournalGenes and Development
Volume13
Issue number9
Publication statusPublished - 1999 May 1
Externally publishedYes

Fingerprint

Single-Stranded DNA
Telomere
Nucleic Acids
RNA Splice Sites
Proteins
DNA
Product Packaging
RNA Recognition Motif
hnRNP A1
Carrier Proteins
Nucleotides
Messenger RNA

Keywords

  • hnRNP A1
  • RNA-recognition motif
  • Telomere
  • X-ray crystallography

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Ding, J., Hayashi, M. K., Zhang, Y., Manche, L., Krainer, A. R., & Xu, R. M. (1999). Crystal structure of the two-RRM domain of hnRNP A1 (UP1) complexed with single-stranded telomeric DNA. Genes and Development, 13(9), 1102-1115.

Crystal structure of the two-RRM domain of hnRNP A1 (UP1) complexed with single-stranded telomeric DNA. / Ding, Jianzhong; Hayashi, Mariko K.; Zhang, Ying; Manche, Lisa; Krainer, Adrian R.; Xu, Rui Ming.

In: Genes and Development, Vol. 13, No. 9, 01.05.1999, p. 1102-1115.

Research output: Contribution to journalArticle

Ding, J, Hayashi, MK, Zhang, Y, Manche, L, Krainer, AR & Xu, RM 1999, 'Crystal structure of the two-RRM domain of hnRNP A1 (UP1) complexed with single-stranded telomeric DNA', Genes and Development, vol. 13, no. 9, pp. 1102-1115.
Ding J, Hayashi MK, Zhang Y, Manche L, Krainer AR, Xu RM. Crystal structure of the two-RRM domain of hnRNP A1 (UP1) complexed with single-stranded telomeric DNA. Genes and Development. 1999 May 1;13(9):1102-1115.
Ding, Jianzhong ; Hayashi, Mariko K. ; Zhang, Ying ; Manche, Lisa ; Krainer, Adrian R. ; Xu, Rui Ming. / Crystal structure of the two-RRM domain of hnRNP A1 (UP1) complexed with single-stranded telomeric DNA. In: Genes and Development. 1999 ; Vol. 13, No. 9. pp. 1102-1115.
@article{4198f5ed49504cb09d1b91b72edddfca,
title = "Crystal structure of the two-RRM domain of hnRNP A1 (UP1) complexed with single-stranded telomeric DNA",
abstract = "Human hnRNP A1 is a versatile single-stranded nucleic acid-binding protein that functions in various aspects of mRNA maturation and in telomere length regulation. The crystal structure of UP1, the amino-terminal domain of human hnRNP A1 containing two RNA-recognition motifs (RRMs), bound to a 12- nucleotide single-stranded telomeric DNA has been determined at 2.1 {\AA} resolution. The structure of the complex reveals the basis for sequence- specific recognition of the single-stranded overhangs of human telomeres by hnRNP A1. It also provides insights into the basis for high-affinity binding of hnRNP A1 to certain RNA sequences, and for nucleic acid binding and functional synergy between the RRMs. In the crystal structure, a UP1 dimer binds to two strands of DNA, and each strand contacts RRM1 of one monomer and RRM2 of the other. The two DNA strands are antiparallel, and regions of the protein flanking each RRM make important contacts with DNA. The extensive protein-protein interface seen in the crystal structure of the protein-DNA complex and the evolutionary conservation of the interface residues suggest the importance of specific protein-protein interactions for the sequence- specific recognition of single-stranded nucleic acids. Models for regular packaging of telomere 3' overhangs and for juxtaposition of alternative 5' splice sites are proposed.",
keywords = "hnRNP A1, RNA-recognition motif, Telomere, X-ray crystallography",
author = "Jianzhong Ding and Hayashi, {Mariko K.} and Ying Zhang and Lisa Manche and Krainer, {Adrian R.} and Xu, {Rui Ming}",
year = "1999",
month = "5",
day = "1",
language = "English",
volume = "13",
pages = "1102--1115",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "9",

}

TY - JOUR

T1 - Crystal structure of the two-RRM domain of hnRNP A1 (UP1) complexed with single-stranded telomeric DNA

AU - Ding, Jianzhong

AU - Hayashi, Mariko K.

AU - Zhang, Ying

AU - Manche, Lisa

AU - Krainer, Adrian R.

AU - Xu, Rui Ming

PY - 1999/5/1

Y1 - 1999/5/1

N2 - Human hnRNP A1 is a versatile single-stranded nucleic acid-binding protein that functions in various aspects of mRNA maturation and in telomere length regulation. The crystal structure of UP1, the amino-terminal domain of human hnRNP A1 containing two RNA-recognition motifs (RRMs), bound to a 12- nucleotide single-stranded telomeric DNA has been determined at 2.1 Å resolution. The structure of the complex reveals the basis for sequence- specific recognition of the single-stranded overhangs of human telomeres by hnRNP A1. It also provides insights into the basis for high-affinity binding of hnRNP A1 to certain RNA sequences, and for nucleic acid binding and functional synergy between the RRMs. In the crystal structure, a UP1 dimer binds to two strands of DNA, and each strand contacts RRM1 of one monomer and RRM2 of the other. The two DNA strands are antiparallel, and regions of the protein flanking each RRM make important contacts with DNA. The extensive protein-protein interface seen in the crystal structure of the protein-DNA complex and the evolutionary conservation of the interface residues suggest the importance of specific protein-protein interactions for the sequence- specific recognition of single-stranded nucleic acids. Models for regular packaging of telomere 3' overhangs and for juxtaposition of alternative 5' splice sites are proposed.

AB - Human hnRNP A1 is a versatile single-stranded nucleic acid-binding protein that functions in various aspects of mRNA maturation and in telomere length regulation. The crystal structure of UP1, the amino-terminal domain of human hnRNP A1 containing two RNA-recognition motifs (RRMs), bound to a 12- nucleotide single-stranded telomeric DNA has been determined at 2.1 Å resolution. The structure of the complex reveals the basis for sequence- specific recognition of the single-stranded overhangs of human telomeres by hnRNP A1. It also provides insights into the basis for high-affinity binding of hnRNP A1 to certain RNA sequences, and for nucleic acid binding and functional synergy between the RRMs. In the crystal structure, a UP1 dimer binds to two strands of DNA, and each strand contacts RRM1 of one monomer and RRM2 of the other. The two DNA strands are antiparallel, and regions of the protein flanking each RRM make important contacts with DNA. The extensive protein-protein interface seen in the crystal structure of the protein-DNA complex and the evolutionary conservation of the interface residues suggest the importance of specific protein-protein interactions for the sequence- specific recognition of single-stranded nucleic acids. Models for regular packaging of telomere 3' overhangs and for juxtaposition of alternative 5' splice sites are proposed.

KW - hnRNP A1

KW - RNA-recognition motif

KW - Telomere

KW - X-ray crystallography

UR - http://www.scopus.com/inward/record.url?scp=0033134777&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033134777&partnerID=8YFLogxK

M3 - Article

C2 - 10323862

AN - SCOPUS:0033134777

VL - 13

SP - 1102

EP - 1115

JO - Genes and Development

JF - Genes and Development

SN - 0890-9369

IS - 9

ER -