Magnetism, originating from the moving charges and spin of elementary particles, has revolutionized important technologies such as data storage and biomedical imaging, and continues to bring forth new phenomena in emergent materials and reduced dimensions. The recently discovered two-dimensional (2D) magnetic van der Waals crystals provide ideal platforms for understanding 2D magnetism, the control of which has been fueling opportunities for atomically thin, flexible magneto-optic and magnetoelectric devices (such as magnetoresistive memories and spin field-effect transistors). The seamless integration of 2D magnets with dissimilar electronic and photonic materials opens up exciting possibilities for unprecedented properties and functionalities. We review the progress in this area and identify the possible directions for device applications, which may lead to advances in spintronics, sensors, and computing.
A human postcatalytic spliceosome structure reveals essential roles of metazoan factors for exon ligation
During exon ligation, the Saccharomyces cerevisiae spliceosome recognizes the 3′-splice site (3’SS) of precursor messenger RNA (pre-mRNA) through non–Watson-Crick pairing with the 5’SS and the branch adenosine, in a conformation stabilized by Prp18 and Prp8. Here we present the 3.3-angstrom cryo–electron microscopy structure of a human postcatalytic spliceosome just after exon ligation. The 3’SS docks at the active site through conserved RNA interactions in the absence of Prp18. Unexpectedly, the metazoan-specific FAM32A directly bridges the 5′-exon and intron 3’SS of pre-mRNA and promotes exon ligation, as shown by functional assays. CACTIN, SDE2, and NKAP—factors implicated in alternative splicing—further stabilize the catalytic conformation of the spliceosome during exon ligation. Together these four proteins act as exon ligation factors. Our study reveals how the human spliceosome has co-opted additional proteins to modulate a conserved RNA-based mechanism for 3’SS selection and to potentially fine-tune alternative splicing at the exon ligation stage.
How hexanucleotide GGGGCC (G4C2) repeat expansions in C9orf72 cause frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) is not understood. We developed a mouse model engineered to express poly(PR), a proline-arginine (PR) dipeptide repeat protein synthesized from expanded G4C2 repeats. The expression of green fluorescent protein–conjugated (PR)50 (a 50-repeat PR protein) throughout the mouse brain yielded progressive brain atrophy, neuron loss, loss of poly(PR)-positive cells, and gliosis, culminating in motor and memory impairments. We found that poly(PR) bound DNA, localized to heterochromatin, and caused heterochromatin protein 1α (HP1α) liquid-phase disruptions, decreases in HP1α expression, abnormal histone methylation, and nuclear lamina invaginations. These aberrations of histone methylation, lamins, and HP1α, which regulate heterochromatin structure and gene expression, were accompanied by repetitive element expression and double-stranded RNA accumulation. Thus, we uncovered mechanisms by which poly(PR) may contribute to the pathogenesis of C9orf72-associated FTD and ALS.