A mixed antagonistic/synergistic miRNA repression model enables accurate predictions of multi-input miRNA sensor activity
- Award ID(s):
- 1745645
- PAR ID:
- 10076209
- Date Published:
- Journal Name:
- Nature Communications
- Volume:
- 9
- Issue:
- 1
- ISSN:
- 2041-1723
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
Abstract Motivation MicroRNAs (miRNAs) are small noncoding RNAs that play important roles in gene regulation and phenotype development. The identification of miRNA transcription start sites (TSSs) is critical to understand the functional roles of miRNA genes and their transcriptional regulation. Unlike protein-coding genes, miRNA TSSs are not directly detectable from conventional RNA-Seq experiments due to miRNA-specific process of biogenesis. In the past decade, large-scale genome-wide TSS-Seq and transcription activation marker profiling data have become available, based on which, many computational methods have been developed. These methods have greatly advanced genome-wide miRNA TSS annotation. Results In this study, we summarized recent computational methods and their results on miRNA TSS annotation. We collected and performed a comparative analysis of miRNA TSS annotations from 14 representative studies. We further compiled a robust set of miRNA TSSs (RSmirT) that are supported by multiple studies. Integrative genomic and epigenomic data analysis on RSmirT revealed the genomic and epigenomic features of miRNA TSSs as well as their relations to protein-coding and long non-coding genes. Contact xiaoman@mail.ucf.edu, haihu@cs.ucf.edumore » « less
-
Abstract The engineering of osteochondral interfaces remains a challenge. MicroRNAs (miRs) have emerged as significant tools to regulate the differentiation and proliferation of osteogenic and chondrogenic formation in the human musculoskeletal system. Here, we describe a novel approach to osteochondral reconstruction based on the three-dimensional (3D) bioprinting of miR-transfected adipose-derived stem cell (ADSC) spheroids to produce a heterotypic interface that addresses the intrinsic limitations of the traditional approach to inducing zonal differentiation via the use of diffusible cytokines. We evaluated the delivery of miR-148b for osteogenic differentiation and the codelivery of miR-140 and miR-21 for the chondrogenic differentiation of ADSC spheroids. Our results demonstrated that miR-transfected ADSC spheroids exhibited upregulated expression of osteogenic and chondrogenic differentiation related gene and protein markers, and enhanced mineralization and cell proliferation compared to spheroids differentiated using a commercially-available differentiation medium. Upon confirmation of the osteogenic and chondrogenic potential of miR-transfected ADSC spheroids, using aspiration-assisted bioprinting, these spheroids were 3D bioprinted into a dual-layer heterotypic osteochondral interface with a stratified arrangement of distinct osteogenic and chondrogenic zones. The proposed approach holds great promise for the biofabrication of stratified tissues, not only for the osteochondral interfaces presented in this work, but also for other composite tissues and tissue interfaces, such as, but not limited to, the bone-tendon-muscle interface and craniofacial tissues.more » « less
-
Helmer-Citterich, Manuela (Ed.)MicroRNAs (miRNAs) play crucial roles in gene regulation. Most studies focus on mature miRNAs, which leaves many unknowns about primary miRNAs (pri-miRNAs). To fill the gap, we attempted to model the expression of pri-miRNAs in 1829 primary cell types, cell lines, and tissues in this study. We demonstrated that the expression of pri-miRNAs can be modeled well by the expression of specific sets of mRNAs, which we termed their associated mRNAs. These associated mRNAs differ from their corresponding target mRNAs and are enriched with specific functions. Most associated mRNAs of a miRNA are shared across conditions, while on average, about one-fifth of the associated mRNAs are condition-specific. Our study shed new light on understanding miRNA biogenesis and general gene transcriptional regulation.more » « less
An official website of the United States government

