Divergent target recognition by coexpressed 5'-isomiRs of miR-142-3p and selective viral mimicry.
RNA
; 21(9): 1606-20, 2015 Sep.
Article
en En
| MEDLINE
| ID: mdl-26137849
ABSTRACT
Sequence heterogeneity at the ends of mature microRNAs (miRNAs) is well documented, but its effects on miRNA function are largely unexplored. Here we studied the impact of miRNA 5'-heterogeneity, which affects the seed region critical for target recognition. Using the example of miR-142-3p, an emerging regulator of the hematopoietic lineage in vertebrates, we show that naturally coexpressed 5'-variants (5'-isomiRs) can recognize largely distinct sets of binding sites. Despite this, both miR-142-3p isomiRs regulate exclusive and shared targets involved in actin dynamics. Thus, 5'-heterogeneity can substantially broaden and enhance regulation of one pathway. Other 5'-isomiRs, in contrast, recognize largely overlapping sets of binding sites. This is exemplified by two herpesviral 5'-isomiRs that selectively mimic one of the miR-142-3p 5'-isomiRs. We hypothesize that other cellular and viral 5'-isomiRs can similarly be grouped into those with divergent or convergent target repertoires, based on 5'-sequence features. Taken together, our results provide a detailed characterization of target recognition by miR-142-3p and its 5'-isomiR-specific viral mimic. We furthermore demonstrate that miRNA 5'-end variation leads to differential targeting and can thus broaden the target range of miRNAs.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
ARN Viral
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Actinas
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Herpesvirus Humano 8
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MicroARNs
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
RNA
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos