Gene of the month:DICER1:ruler and controller

Journal of Clinical Pathology - Tập 74 Số 2 - Trang 69-72 - 2021
Michelle Thunders1, Brett Delahunt2
1Pathology and Molecular Medicine, University of Otago, Wellington 6242, New Zealand
2Pathology and Molecular Medicine, University of Otago, Wellington, New Zealand

Tóm tắt

DICER1 is a highly conserved RNaseIII endoribonuclease that has a critical role in the biogenesis of microRNAs (miRNAs). miRNAs are small regulatory RNAs responsible for post-transcriptional gene silencing, controlling more than half of human protein-coding genes. This is achieved through the targeting and regulation of complementary RNA transcripts and has a well-documented role in post-transcriptional gene regulation and transposon repression. DICER1 deficiency results in dysregulation of miRNAs, changing the expression of many genes. DICER1 syndrome represents a collection of benign and malignant tumours arising from an autosomally inherited germline mutation leading to an inherited predisposition to cancer. The syndrome represents an unusual form of Knudson’s two-hit hypothesis, where individuals with a pathogenic germlineDICER1variant acquire a second trans-somatic missenseDICER1mutation. This somatic mutation appears to have to occur in one of five hotspots codons and may contribute towards the incomplete penetrance observed within DICER1 syndrome families. In this case, DICER1 is haploinsuffcient with only one deletion required and partial loss of function being advantageous to tumours over complete loss of function. As increasing data emerge reaffirming the pivotal role of DICER1 in the maintenance of human physiology,DICER1is likely to become an increasingly attractive target for novel therapeutic strategies.

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Journal of Clinical Pathology

Tập 74 Số 2

69-72

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