1,720,959 research outputs found
The emerging role of RNA modifications in the regulation of mRNA stability
No full textMany studies have highlighted the importance of the tight regulation of mRNA stability in the control of gene expression. mRNA stability largely depends on the mRNA nucleotide sequence, which affects the secondary and tertiary structures of the mRNAs, and the accessibility of various RNA-binding proteins to the mRNAs. Recent advances in high-throughput RNA-sequencing techniques have resulted in the elucidation of the important roles played by mRNA modifications and mRNA nucleotide sequences in regulating mRNA stability. To date, hundreds of different RNA modifications have been characterized. Among them, several RNA modifications, including N-6-methyladenosine (m(6)A), N-6,2 '-O-dimethyladenosine (m(6)Am), 8-oxo-7,8-dihydroguanosine (8-oxoG), pseudouridine (psi), 5-methylcytidine (m(5)C), and N-4-acetylcytidine (ac(4)C), have been shown to regulate mRNA stability, consequently affecting diverse cellular and biological processes. In this review, we discuss our current understanding of the molecular mechanisms underlying the regulation of mammalian mRNA stability by various RNA modifications.
m(1)A and m(6)A modifications function cooperatively to facilitate rapid mRNA degradation
No full textN-6-Methyladenosine (m(6)A), the most abundant internal mRNA modification, affects multiple steps in gene expression. Mechanistically, the binding of YTHDF2 to m(6)A on mRNAs elicits rapid mRNA degradation by re-cruiting several RNA degrading enzymes. Here, we show that N-1-methyladenosine (m(1)A), another type of RNA modification, accelerates rapid m(6)A RNA degradation. We identify HRSP12 as an RNA-binding protein that recognizes m(1)A. The binding of HRSP12 to m(1)A promotes efficient interaction of YTHDF2 with m(6)A, consequently facilitating endoribonucleolytic cleavage via the RNase P/MRP complex. Transcriptomewide analyses also reveal that mRNAs harboring both m(1)A and m(6)A are downregulated in an HRSP12-dependent manner compared with mRNAs harboring m(6)A only. Accordingly, a subset of endogenous circular RNAs that harbor m(6)A and associate with YTHDF2 in an HRSP12-dependent manner is also subjected to m(1)A-facilitated rapid degradation. Together, our observations provide compelling evidence for crosstalk between different RNA modifications.
UPF1 promotes rapid degradation of m(6)A-containing RNAs
No full textN-6-methyladenosine (m(6)A) is the most prevalent internal modification in eukaryotic mRNAs and affects RNA processing and metabolism. When YTHDF2, an m(6)A-recognizing protein, binds to m(6)A, it facilitates the destabilization of m(6)A-containing RNAs (m(6)A RNAs). Here, we demonstrate that upstream frameshift 1 (UPF1), a key factor for nonsense-mediated mRNA decay, interacts with YTHDF2, thereby triggering rapid degradation of m(6)A RNAs. The UPF1-mediated m(6)A RNA degradation depends on a specific interaction between UPF1 and N-terminal residues 101-168 of YTHDF2. UPF1 ATPase/helicase activities, and UPF1 interaction with proline-rich nuclear receptor coactivator 2 (PNRC2), a decapping-promoting factor preferentially involved in nonsense-mediated mRNA decay. Furthermore, transcriptome-wide analyses show that YTHDF2-bound mRNAs that are not substrates for HRSP12-RNase P/MRP-mediated endoribonucleolytic cleavage are destabilized with a higher dependency on UPF1. Collectively, our data indicate dynamic and multilayered regulation of the stability of m(6)A RNAs and highlight the multifaceted role of UPF1 in mRNA decay.
Endoribonucleolytic Cleavage of m(6)A-Containing RNAs by RNase P/MRP Complex
No full textN-6-methyladenosine (m(6)A) is the most abundant internal modification in RNAs and plays regulatory roles in a variety of biological and physiological processes. Despite its important roles, the molecular mechanism underlying m(6)A-mediated gene regulation is poorly understood. Here, we show that m(6)A-containing RNAs are subject to endoribonucleolytic cleavage via YTHDF2 (m(6)A reader protein), HRSP12 (adaptor protein), and RNase P/MRP (endoribonucleases). We demonstrate that HRSP12 functions as an adaptor to bridge YTHDF2 and RNase P/MRP, eliciting rapid degradation of YTHDF2-bound RNAs. Transcriptome-wide analyses show that m(6)A RNAs that are preferentially targeted for endoribonucleolytic cleavage have an HRSP12-binding site and a RNase P/MRP-directed cleavage site upstream and downstream of the YTHDF2-binding site, respectively. We also find that a subset of m(6)A-containing circular RNAs associates with YTHDF2 in an HRSP12-dependent manner and is selectively downregulated by RNase P/MRP. Thus, our data expand the known functions of RNase P/MRP to endoribonucleolytic cleavage of m(6)A RNAs.
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Ribonuclease that promotes longevity by cleaving age-dependently accumulating circular RNAs
No full textVariations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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