Regulation of MicroRNA Expression and Abundance during Lymphopoiesis

Genomics and Immunity, NIAMS, NIH, Bethesda, MD 20892, USA.
Immunity (Impact Factor: 21.56). 06/2010; 32(6):828-39. DOI: 10.1016/j.immuni.2010.05.009
Source: PubMed


Although the cellular concentration of miRNAs is critical to their function, how miRNA expression and abundance are regulated during ontogeny is unclear. We applied miRNA-, mRNA-, and ChIP-Seq to characterize the microRNome during lymphopoiesis within the context of the transcriptome and epigenome. We show that lymphocyte-specific miRNAs are either tightly controlled by polycomb group-mediated H3K27me3 or maintained in a semi-activated epigenetic state prior to full expression. Because of miRNA biogenesis, the cellular concentration of mature miRNAs does not typically reflect transcriptional changes. However, we uncover a subset of miRNAs for which abundance is dictated by miRNA gene expression. We confirm that concentration of 5p and 3p miRNA strands depends largely on free energy properties of miRNA duplexes. Unexpectedly, we also find that miRNA strand accumulation can be developmentally regulated. Our data provide a comprehensive map of immunity's microRNome and reveal the underlying epigenetic and transcriptional forces that shape miRNA homeostasis.

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Available from: Zhiyu Li
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    • "Recent studies have revealed the critical role of miRNAs in tuning immunity. Immune cells express unique miRNA profiles which contribute to their respective functions (Kuchen et al., 2010) and change their miRNA repertoires in response to varying stimuli such as T cell receptor (TCR) activation (Bronevetsky et al., 2013). The past decade has seen many fascinating discoveries about the role of miRNAs in immunity. "
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    • "MiR- 27 is ubiquitously expressed in many tissues and cell types. However, T cells express the highest levels of miR-27 (Kuchen et al., 2010), suggesting that miR-27 functions in regulating T cell responses. T cell receptor/CD3 complex (TCR) signaling is important for proliferation, differentiation, and cell death during T cell development ; it also contributes to clonal expansion and effector cytokine secretion during T cell activation (Murphy et al., 2008). "
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    • "Also, differences in circulating miRNAs that are expressed at low levels may have been missed. Other techniques that are not limited in the number of miRNAs, such as small RNA sequencing using deep sequencing platforms, have been shown to be very useful to investigate this [39,40]. Besides the use of a different analytical platform, one might also consider using PAXgene blood instead of plasma. "
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