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The structure of the METTL3-METTL14 complex, which mediates N.sup.6-adenosine methylation of RNA, suggests that the METTL3 subunit is the catalytic core while METTL14 serves to bind RNA. A window on m.sup.6A epitranscriptomics The various base modifications now known to occur in messenger RNA and long non-coding RNA are reversible, and are utilized to dynamically modify the function of the RNA. The N.sup.6-methyladenosine modification is removed by an enzyme complex comprising METTL3 and METTL14. Ping Yin and colleagues have solved structures of the methyltransferase domains of this heterodimeric complex with and without ligand. Surprisingly, the S-adenosyl methionine ligand was found only the METTL3 pocket, not in METTL14. This suggests a model in which there is a single catalytic subunit, with METTL3 functioning as an RNA binding platform. The reported structures provide unprecedented mechanistic insight into m.sup.6A RNA methylation and suggest new opportunities for the development of therapeutic agents. Chemical modifications of RNA have essential roles in a vast range of cellular processes.sup.1,2,3. N.sup.6-methyladenosine (m.sup.6A) is an abundant internal modification in messenger RNA and long non-coding RNA that can be dynamically added and removed by RNA methyltransferases (MTases) and demethylases, respectively.sup.2,3,4,5. An MTase complex comprising methyltransferase-like 3 (METTL3) and methyltransferase-like 14 (METTL14) efficiently catalyses methyl group transfer.sup.6,7. In contrast to the well-studied DNA MTase.sup.8, the exact roles of these two RNA MTases in the complex remain to be elucidated. Here we report the crystal structures of the METTL3-METTL14 heterodimer with MTase domains in the ligand-free, S-adenosyl methionine (AdoMet)-bound and S-adenosyl homocysteine (AdoHcy)-bound states, with resolutions of 1.9, 1.71 and 1.61 Å, respectively. Both METTL3 and METTL14 adopt a class I MTase fold and they interact with each other via an extensive hydrogen bonding network, generating a positively charged groove. Notably, AdoMet was observed in only the METTL3 pocket and not in METTL14. Combined with biochemical analysis, these results suggest that in the m.sup.6A MTase complex, METTL3 primarily functions as the catalytic core, while METTL14 serves as an RNA-binding platform, reminiscent of the target recognition domain of DNA N.sup.6-adenine MTase.sup.9,10. This structural information provides an important framework for the functional investigation of m.sup.6A., Author(s): Xiang Wang [sup.1] , Jing Feng [sup.1] , Yuan Xue [sup.1] , Zeyuan Guan [sup.1] , Delin Zhang [sup.1] , Zhu Liu [sup.2] , Zhou Gong [sup.3] , Qiang [...]

N6-methyldeoxyadenine (6mA) has recently been reported as a prevalent DNA modification in eukaryotes. The Tetrahymena thermophila MTA1 complex consisting of four subunits, namely MTA1, MTA9, p1, and p2, is the first identified eukaryotic 6mA methyltransferase (MTase) complex. Unlike the prokaryotic 6mA MTases which have been biochemically and structurally characterized, the operation mode of the MTA1 complex remains largely elusive. Here, we report the cryogenic electron microscopy structures of the quaternary MTA1 complex in S-adenosyl methionine (SAM)-bound (2.6 Å) and S-adenosyl homocysteine (SAH)-bound (2.8 Å) states. Using an AI-empowered integrative approach based on AlphaFold prediction and chemical cross-linking mass spectrometry, we further modeled a near-complete structure of the quaternary complex. Coupled with biochemical characterization, we revealed that MTA1 serves as the catalytic core, MTA1, MTA9, and p1 likely accommodate the substrate DNA, and p2 may facilitate the stabilization of MTA1. These results together offer insights into the molecular mechanism underpinning methylation by the MTA1 complex and the potential diversification of MTases for N6-adenine methylation. [ABSTRACT FROM AUTHOR]

Various kinds of cap structures, such as m7G, triphosphate groups, NAD and dpCoA, protect the 5′ terminus of RNA. The cap structures bond covalently to RNA and affect its stability, translation, and transport. The removal of the caps is mainly executed by Nudix hydrolase family proteins, including Dcp2, RppH and NudC. Numerous efforts have been made to elucidate the mechanism underlying the removal of m7G, triphosphate group, and NAD caps. In contrast, few studies related to the cleavage of the RNA dpCoA cap have been conducted. Here, we report the hydrolytic activity of Escherichia coli NudC towards dpCoA and dpCoA-capped RNA in vitro. We also determined the crystal structure of dimeric NudC in complex with dpCoA at 2.0 Å resolution. Structural analysis revealed that dpCoA is recognized and hydrolysed in a manner similar to NAD. In addition, NudC may also remove other dinucleotide derivative caps of RNA, which comprise the AMP moieties. NudC homologs in Saccharomyces cerevisiae and Arabidopsis thaliana exhibited similar dpCoA decapping (deCoAping) activity. These results together indicate a conserved mechanism underpinning the hydrolysis of dpCoA-capped RNA in both prokaryotes and eukaryotes. [ABSTRACT FROM AUTHOR]

Unidirectional spin Hall magnetoresistance (USMR) is a magnetoresistance effect with potential applications to read two-terminal spin–orbit-torque (SOT) devices directly. In this work, we observed a large USMR value (up to 0.7 × 10−11 per A/cm2, 50% larger than reported values from heavy metals) in sputtered amorphous PtSn4/CoFeB bilayers. Ta/CoFeB bilayers with interfacial MgO insertion layers are deposited as control samples. The control experiments show that increasing the interfacial resistance can increase the USMR value, which is the case in PtSn4/CoFeB bilayers. The observation of a large USMR value in an amorphous spin–orbit-torque material has provided an alternative pathway for USMR application in two-terminal SOT devices. [ABSTRACT FROM AUTHOR]

Interlayer exchange coupling in polycrystalline Co2FeAl/Cr/Co2FeAl multilayers with Ta and MgO capping layers is investigated. Compared with Ta‐capped samples, the MgO capping layer induces the oscillatory coupling periods, ≈2.1 nm for Si substrate and ≈4.0 and ≈1.9 nm for SiO2 substrate. The oscillatory coupling period originates from the formation of quantum well states at the Cr/Co2FeAl interface due to the MgO capping layer. Meanwhile, Δ1 Bloch state in the majority spin and Δ2' Bloch state in the minority spin contribute to the short (≈2.1 and ≈1.9 nm) and long oscillatory period (≈4.0 nm) in the disordered B2 Co2FeAl multilayers, respectively. [ABSTRACT FROM AUTHOR]

Author(s): Xiang Wang; Jing Feng; Yuan Xue; Zeyuan Guan; Delin Zhang; Zhu Liu; Zhou Gong; Qiang Wang; Jinbo Huang; Chun Tang; Tingting Zou; Ping Yin Nature 534, 575578 (2016);doi:10.1038/nature18298 In [...]