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Eric A Miska

Publications and source records attributed to Eric A Miska.

8 recordsLinked to original sources
PubMed2025

Transposable Elements Drive Regulatory and Functional Innovation of F-box Genes.

Protein domains of transposable elements (TEs) and viruses increase the protein diversity of host genomes by recombining with other protein domains. By screening 10 million eukaryotic proteins, we identified several domains that define multicopy gene families and frequently co-occur with TE/viral domains. Among these, a Tc1/Mariner transposase helix-turn-helix (HTH) domain was captured by F-box genes in the Caenorhabditis genus, creating a new class of F-box genes. For specific members of this class, like fbxa-215, we found that the HTH domain is required for diverse processes including germ granule localization, fertility, and thermotolerance. Furthermore, we provide evidence that Heat Shock Factor 1 (HSF-1) mediates the transcriptional integration of fbxa-215 into the heat shock response by binding to Helitron TEs directly upstream of the fbxa-215 locus. The interactome of HTH-bearing F-box factors suggests roles in post-translational regulation and proteostasis, consistent with established functions of F-box proteins. Based on AlphaFold2 multimer proteome-wide screens, we propose that the HTH domain may diversify the repertoire of protein substrates that F-box factors regulate post-translationally. We also describe an independent capture of a TE domain by F-box genes in zebrafish. In conclusion, we identify two independent TE domain captures by F-box genes in eukaryotes and provide insights into how these novel proteins are integrated within host gene regulatory networks.

Animals↗
PubMed2005

MicroRNA expression profiles classify human cancers.

Recent work has revealed the existence of a class of small non-coding RNA species, known as microRNAs (miRNAs), which have critical functions across various biological processes. Here we use a new, bead-based flow cytometric miRNA expression profiling method to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers. The miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours. We observe a general downregulation of miRNAs in tumours compared with normal tissues. Furthermore, we were able to successfully classify poorly differentiated tumours using miRNA expression profiles, whereas messenger RNA profiles were highly inaccurate when applied to the same samples. These findings highlight the potential of miRNA profiling in cancer diagnosis.

Animals↗
PubMed2005

The let-7 MicroRNA family members mir-48, mir-84, and mir-241 function together to regulate developmental timing in Caenorhabditis elegans.

The microRNA let-7 is a critical regulator of developmental timing events at the larval-to-adult transition in C. elegans. Recently, microRNAs with sequence similarity to let-7 have been identified. We find that doubly mutant animals lacking the let-7 family microRNA genes mir-48 and mir-84 exhibit retarded molting behavior and retarded adult gene expression in the hypodermis. Triply mutant animals lacking mir-48, mir-84, and mir-241 exhibit repetition of L2-stage events in addition to retarded adult-stage events. mir-48, mir-84, and mir-241 function together to control the L2-to-L3 transition, likely by base pairing to complementary sites in the hbl-1 3' UTR and downregulating hbl-1 activity. Genetic analysis indicates that mir-48, mir-84, and mir-241 specify the timing of the L2-to-L3 transition in parallel to the heterochronic genes lin-28 and lin-46. These results indicate that let-7 family microRNAs function in combination to affect both early and late developmental timing decisions.

Animals↗
PubMed2005

How microRNAs control cell division, differentiation and death.

After the milestone discovery of the first microRNA in 1993, the past five years have seen a phenomenal surge of interest in these short, regulatory RNAs. Given that 2% of all known human genes encode microRNAs, one main goal is to uncover microRNA function. Although it has been more difficult to assign function to microRNAs in animals than it has been in plants, important roles are emerging: in invertebrates, microRNAs control developmental timing, neuronal differentiation, tissue growth and programmed cell death. Functional studies in zebrafish and mice point toward important roles for microRNAs during morphogenesis and organogenesis. Finally, microRNAs might regulate viral infection and human cancer.

Animals↗
PubMed2005

MicroRNA functions in animal development and human disease.

Five years into the 'small RNA revolution' it is hard not to share in the excitement about the rapidly unravelling biology of microRNAs. Since the discovery of the first microRNA gene, lin-4, in the nematode Caenorhabditis elegans, many more of these short regulatory RNA genes have been identified in flowering plants, worms, flies, fish, frogs and mammals. Currently, about 2% of the known human genes encode microRNAs. MicroRNAs are essential for development and this review will summarise our current knowledge of animal microRNA function. We will also discuss the emerging links of microRNA biology to stem cell research and human disease, in particular cancer.

Animals↗
PubMed2004

Microarray analysis of microRNA expression in the developing mammalian brain.

BACKGROUND: MicroRNAs are a large new class of tiny regulatory RNAs found in nematodes, plants, insects and mammals. MicroRNAs are thought to act as post-transcriptional modulators of gene expression. In invertebrates microRNAs have been implicated as regulators of developmental timing, neuronal differentiation, cell proliferation, programmed cell death and fat metabolism. Little is known about the roles of microRNAs in mammals. RESULTS: We isolated 18-26 nucleotide RNAs from developing rat and monkey brains. From the sequences of these RNAs and the sequences of the rat and human genomes we determined which of these small RNAs are likely to have derived from stem-loop precursors typical of microRNAs. Next, we developed a microarray technology suitable for detecting microRNAs and printed a microRNA microarray representing 138 mammalian microRNAs corresponding to the sequences of the microRNAs we cloned as well as to other known microRNAs. We used this microarray to determine the profile of microRNAs expressed in the developing mouse brain. We observed a temporal wave of expression of microRNAs, suggesting that microRNAs play important roles in the development of the mammalian brain. CONCLUSION: We describe a microarray technology that can be used to analyze the expression of microRNAs and of other small RNAs. MicroRNA microarrays offer a new tool that should facilitate studies of the biological roles of microRNAs. We used this method to determine the microRNA expression profile during mouse brain development and observed a temporal wave of gene expression of sequential classes of microRNAs.

Animals↗
PubMed2002

Acetylation of beta-catenin by CREB-binding protein (CBP).

Acetylation controls the activity of numerous proteins involved in regulating gene transcription as well as many other cellular processes. In this report we show that the CREB-binding protein (CBP) acetyltransferase acetylates beta-catenin protein in vivo. beta-Catenin is a central component of the Wnt signaling pathway, which is of key importance in development as well as being heavily implicated in a variety of human cancers. We show that the CBP-mediated acetylation of beta-catenin occurs at a single site, lysine 49. Importantly, this lysine is frequently found mutated in cancer and is in a region of importance to the regulation of beta-catenin. We show that mutation of this site leads specifically to an increase in the ability of beta-catenin to activate the c-myc gene but not other beta-catenin-regulated genes. This suggests that acetylation of beta-catenin is involved in regulating Wnt signaling in a promoter-specific fashion.

Acetylation↗