Signal Transduction

See-Saw Gene Expression

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Science  15 Mar 2013:
Vol. 339, Issue 6125, pp. 1253
DOI: 10.1126/science.339.6125.1253-b

Upon wounding, the body must act quickly to initiate a repair or regeneration response. Using a human-skin ex vivo organ-culture system, Sundaram et al. found that the small noncoding RNA miR-198, which is encoded in the 3′ untranslated region of follistatin-like 1 (FSTL1), is expressed at high levels in healthy epidermis but is suppressed after wounding. FSTL1 showed the opposite pattern of expression. Knockdown studies demonstrated that FSTL1 promoted keratinocyte migration, which is important for wound healing, whereas miR-198 suppressed this. Examination of chronic nonhealing ulcer wounds from individuals with diabetes mellitus revealed that miR-198 rather than FSTL1 was expressed, which explains the lack of keratinocyte migration and tissue repair seen in these lesions. A posttranscriptional regulatory mechanism allows for this "see-saw" pattern of expression: Transforming growth factor- 1 helped to stabilize FSTL1 by down-regulating the splicing regulatory protein KSRP, which is necessary for miR-198 expression.

Nature 10.1038/nature11890 (2013).

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