Selective degradation of early-response-gene mRNAs: functional analyses of sequence features of the AU-rich elements.

摘要: The metabolic lifetime of mRNA can be specified by specific cis-acting elements within mRNA. One type element is an adenylate- and uridylate-rich (ARE) found in the 3' untranslated region many highly unstable mRNAs for mammalian early-response genes (ERGs). Among better-characterized members ERG family are certain encoding nuclear transcription factors. Of particular significance was finding that their decay rapidly with kinetics similar to those c-fos Our previous studies ARE-directed have revealed existence this ARE two structurally distinct functionally interdependent domains, termed domain I II. We proposed a two-step mechanism which rapid shortening poly(A) tail leads body further hypothesized general AREs mediate degradation. To test hypothesis address generality critical structural characteristics ARE, RNA-destabilizing functions more than 10 different AU-rich sequences from various factor been tested. Consistent above-mentioned observation carrying functional display biphasic decay, characteristic mechanism. results indicated presence AUUUA pentanucleotides does not always guarantee function region. also led identification novel class destabilizing contains no pentanucleotide. sequence comparison tests continuous U-rich unique feature among AREs. Finally, our experiments showed II has RNA decay-enhancing ability upon its fusion heterologous regions defined first time element, we RDE element.