A Z-DNA binding domain present in the human editing enzyme, double-stranded RNA adenosine deaminase

Proceedings of the National Academy of Sciences of the United States of America - Tập 94 Số 16 - Trang 8421-8426 - 1997
Alan Herbert1, Jens Alfken1, Yang‐Gyun Kim1, Shahzad I. Mian1, Kazuko Nishikura1, Alexander Rich1
1Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139; Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720; and The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104

Tóm tắt

Editing of RNA changes the read-out of information from DNA by altering the nucleotide sequence of a transcript. One type of RNA editing found in all metazoans uses double-stranded RNA (dsRNA) as a substrate and results in the deamination of adenosine to give inosine, which is translated as guanosine. Editing thus allows variant proteins to be produced from a single pre-mRNA. A mechanism by which dsRNA substrates form is through pairing of intronic and exonic sequences before the removal of noncoding sequences by splicing. Here we report that the RNA editing enzyme, human dsRNA adenosine deaminase (DRADA1, or ADAR1) contains a domain (Zα) that binds specifically to the left-handed Z-DNA conformation with high affinity (KD= 4 nM). As formation of Z-DNAin vivooccurs 5′ to, or behind, a moving RNA polymerase during transcription, recognition of Z-DNA by DRADA1 provides a plausible mechanism by which DRADA1 can be targeted to a nascent RNA so that editing occurs before splicing. Analysis of sequences related to Zα has allowed identification of motifs common to this class of nucleic acid binding domain.

Từ khóa


Tài liệu tham khảo

B L Bass The RNA World, eds R F Gesteland, J F Atkins (Cold Spring Harbor Lab. Press, Plainview, NY), pp. 383–418 (1993).

10.1126/science.1710829

10.1126/science.1653450

10.1016/0092-8674(91)90568-J

10.1016/0896-6273(93)90336-P

10.1126/science.7992055

10.1038/387303a0

10.1006/jmbi.1996.0365

10.1073/pnas.91.24.11457

10.1128/MCB.15.3.1389

10.1128/MCB.15.10.5376

10.1002/j.1460-2075.1996.tb00331.x

10.1038/379460a0

10.1074/jbc.271.21.12221

10.1128/MCB.17.5.2413

10.1016/S0021-9258(17)36972-7

10.1074/jbc.271.50.31795

10.1074/jbc.270.29.17098

10.1093/nar/21.11.2669

10.1021/bi00296a009

10.1080/07391102.1983.10507467

10.1016/S0021-9258(18)33681-0

10.1073/pnas.92.16.7550

10.1073/pnas.78.3.1619

10.1006/jmbi.1994.1170

10.1016/S0021-9258(19)84581-7

M Polymentis, B D Stollar J Immunol 154, 2198–2208 (1995).

10.1016/S0022-2836(05)80360-2

10.1006/jmbi.1994.1104

T L Bailey, C Elkan Proceedings of the Second International Conference on Intelligent Systems for Molecular Biology (AAAI Press, Menlo Park, CA), pp. 28–36 (1994).

10.1002/pro.5560051116

10.1002/prot.340190108

10.1006/geno.1994.1018

10.1093/nar/24.19.3836

10.1126/science.1653449

10.1038/379746a0

10.1038/379694a0

10.1016/0092-8674(95)90189-2

10.1038/362219a0

10.1038/364412a0

10.1016/S0969-2126(94)00107-3

10.1002/j.1460-2075.1994.tb06709.x

10.1038/380456a0

10.1016/0925-4773(96)00539-4

10.1021/bi00415a052

10.1016/S0092-8674(00)81824-3

10.1038/282680a0

10.1038/290672a0

10.1073/pnas.79.15.4560

10.1073/pnas.84.20.7024

10.1126/science.2678475

10.1002/j.1460-2075.1992.tb05567.x

S Wolfl, W Vahrson, A G Herbert DNA and Nucleoprotein Structure in Vivo, eds H P Saluz, K Wiebauer (Landes, Austin, TX), pp. 137–159 (1995).

10.1074/jbc.271.20.11595

10.1126/science.7973627

10.1016/0092-8674(95)90532-4

10.1080/07391102.1992.10507985

10.1021/bi00134a026

10.1016/0092-8674(93)90622-W

10.1073/pnas.91.22.10270

10.1073/pnas.93.5.1875

10.1073/pnas.88.6.2259

10.1016/S0021-9258(19)49776-7

10.1016/0168-9525(96)81375-8

Thông tin
Thông tin xuất bản

Proceedings of the National Academy of Sciences of the United States of America

Tập 94 Số 16

8421-8426

Thông tin tác giả