"Lock and key" recognition in the world of protein-RNA interactions: How ADAR2 binds RNA
| Autoři | |
|---|---|
| Rok publikování | 2006 |
| Druh | Článek ve sborníku |
| Konference | xxx |
| Fakulta / Pracoviště MU | |
| Citace | |
| Obor | Biochemie |
| Klíčová slova | NMR; protein-RNA interactions; gene regulation; structure |
| Popis | The association of RNA-binding proteins with RNA transcript begins during transcription. Some of these early-binding proteins remain bound to RNA until it is degraded whereas others recognize and transiently bind to RNA during its maturation for specific processes such as splicing, processing, transport and localization. Some RNA-binding proteins function as RNA chaperones by helping the RNA, which is initially single-stranded, to form various secondary and tertiary structures. When folded these structured RNAs together with specific RNA sequences act as a signal for gene regulation. Adenosine deaminase that acts on RNA (ADAR) is a gene regulator that site-selectively modifies adenosines to inosines within RNA transcripts, thereby recoding genomic information. ADAR selects its substrate for deamination through recognition of certain double-helical irregularities within folded RNA transcript. This recognition is mediated using double-stranded RNA-binding motifs (dsRBMs) of ADAR. It will be demonstrated how ADAR dsRBMs bind a 71 nucleotide RNA encoding the R/G site of the glutamate-activated cation channel. We will show that each dsRBM binds a different structural element of the RNA substrate. ADAR dsRBM1 binds preferentially a stem capped by a pentaloop and ADAR dsRBM2 recognizes a stem containing two AC mismatches. Our structural and functional studies demonstrate that dsRBM, a motive known to bind any RNA duplexes with no sequence specificity, can preferentially bind certain RNA structures and thus mediates site-specific gene regulation. |
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