The epitranscriptomics field has undergone an enormous expansion in the last few years; however, a major limitation is the lack of generic methods to map RNA modifications transcriptome-wide. Here, we show that using direct RNA sequencing, N6-methyladenosine (m6A) RNA modifications can be detected with high accuracy, in the form of systematic errors and decreased base-calling qualities. Specifically, we find that our algorithm, trained with m6A-modified and unmodified synthetic sequences, can predict m6A RNA modifications with ~90% accuracy. We then extend our findings to yeast data sets, finding that our method can identify m6A RNA modifications in vivo with an accuracy of 87%. Moreover, we further validate our method by showing that these ‘errors’ are typically not observed in yeast ime4-knockout strains, which lack m6A modifications. Our results open avenues to investigate the biological roles of RNA modifications in their native RNA context.

Two issues long debated among Pacific and American prehistorians are ( i ) whether there was a pre-Columbian introduction of chicken ( Gallus gallus ) to the Americas and ( ii ) whether Polynesian contact with South America might be identified archaeologically, through the recovery of remains of unquestionable Polynesian origin. We present a radiocarbon date and an ancient DNA sequence from a single chicken bone recovered from the archaeological site of El Arenal-1, on the Arauco Peninsula, Chile. These results not only provide firm evidence for the pre-Columbian introduction of chickens to the Americas, but strongly suggest that it was a Polynesian introduction.

Nanopore RNA sequencing shows promise as a method for discriminating and identifying different RNA modifications in native RNA. Expanding on the ability of nanopore sequencing to detect N6-methyladenosine (m6A), we show that other modifications, in particular pseudouridine (Ѱ) and 2'-O-methylation (Nm), also result in characteristic base-calling 'error' signatures in the nanopore data. Focusing on Ѱ modification sites, we detect known and uncover previously unreported Ѱ sites in mRNAs, ncRNAs and rRNAs, including a Pus4dependent Ѱ modification in yeast mitochondrial rRNA. To explore the dynamics of pseudouridylation, we treat yeast cells with oxidative, cold and heat stresses and detect heatsensitive Ѱ-modified sites in snRNAs, snoRNAs and mRNAs. Finally, we develop a software, nanoRMS, that estimates per-site modification stoichiometries by identifying single-molecule reads with altered current intensity and trace profiles. This work demonstrates that Nm and Ѱ RNA modifications can be detected in cellular RNAs and that Ѱ RNA can be identified in a quantitative manner by nanopore sequencing of native RNA.

JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org.

This paper presents an optimal control design for currentfed induction motor drives. The problem to be considered is to find a feedback control that minimizes a generalized convex energy cost function including the stored magnetic energy and the coil losses, while satisfying torque tracking control objectives. Necessary and sufficient conditions for optimality are established. It is shown here that all the stationary solutions can be obtained analytically and are uniquely defined. It is also shown that closed-forms for dynamic suboptimal solutions can also be obtained. The optimal solutions turn out to imply nonstandard timevarying (reference depending) norm flux operations in opposition to well established field-oriented control that operates with constant flux norm.

No abstract

Background: RNA modifications play central roles in cellular fate and differentiation. However, the machinery responsible for placing, removing, and recognizing more than 170 RNA modifications remains largely uncharacterized and poorly annotated, and we currently lack integrative studies that identify which RNA modificationrelated proteins (RMPs) may be dysregulated in each cancer type. Results: Here, we perform a comprehensive annotation and evolutionary analysis of human RMPs, as well as an integrative analysis of their expression patterns across 32 tissues, 10 species, and 13,358 paired tumor-normal human samples. Our analysis reveals an unanticipated heterogeneity of RMP expression patterns across mammalian tissues, with a vast proportion of duplicated enzymes displaying testisspecific expression, suggesting a key role for RNA modifications in sperm formation and possibly intergenerational inheritance. We uncover many RMPs that are dysregulated in various types of cancer, and whose expression levels are predictive of cancer progression. Surprisingly, we find that several commonly studied RNA modification enzymes such as METTL3 or FTO are not significantly upregulated in most cancer types, whereas several less-characterized RMPs, such as LAGE3 and HENMT1, are dysregulated in many cancers. Conclusions: Our analyses reveal an unanticipated heterogeneity in the expression patterns of RMPs across mammalian tissues and uncover a large proportion of dysregulated RMPs in multiple cancer types. We provide novel targets for future cancer research studies targeting the human epitranscriptome, as well as foundations to understand cell type-specific behaviors that are orchestrated by RNA modifications.

ABSTRACTBackgroundRNA modifications play central roles in cellular fate and differentiation. These features have placed the epitranscriptome in the forefront of developmental biology and cancer research. However, the machinery responsible for placing, removing and recognizing more than 170 RNA modifications remains largely uncharacterized and poorly annotated, and we currently lack integrative studies that identify which RNA modification–related proteins (RMPs) may be dysregulated in each cancer type.ResultsHere we have performed a comprehensive annotation and evolutionary analysis of human RMPs as well as an integrative analysis of their expression patterns across 32 tissues, 10 species and 13,358 paired tumor-normal human samples. Our analysis reveals an unanticipated heterogeneity of RMP expression patterns across mammalian tissues, with a vast proportion of duplicated enzymes displaying testis-specific expression, suggesting a key role for RNA modifications in sperm formation and possibly intergenerational inheritance. Moreover, through the analysis of paired tumor-normal human samples we uncover many RMPs that are dysregulated in various types of cancer, and whose expression levels are predictive of cancer progression. Surprisingly, we find that several commonly studied RNA modification enzymes such as METTL3 or FTO, are not significantly up-regulated in most cancer types, once the sample is properly scaled and normalized to the full dataset, whereas several less-characterized RMPs, such as LAGE3 and HENMT1, are dysregulated in many cancers.ConclusionsOur analyses reveal an unanticipated heterogeneity in the expression patterns of RMPs across mammalian tissues, and uncover a large proportion of dysregulated RMPs in multiple cancer types. We provide novel targets for future cancer research studies targeting the human epitranscriptome, as well as foundations to understand cell type-specific behaviours that are orchestrated by RNA modifications.