RNA binding proteins (RBPs) orchestrate the production, processing, and function of mRNAs. Here, we present the affinity landscapes of 78 human RBPs using an unbiased assay that determines the ...sequence, structure, and context preferences of these proteins in vitro by deep sequencing of bound RNAs. These data enable construction of “RNA maps” of RBP activity without requiring crosslinking-based assays. We found an unexpectedly low diversity of RNA motifs, implying frequent convergence of binding specificity toward a relatively small set of RNA motifs, many with low compositional complexity. Offsetting this trend, however, we observed extensive preferences for contextual features distinct from short linear RNA motifs, including spaced “bipartite” motifs, biased flanking nucleotide composition, and bias away from or toward RNA structure. Our results emphasize the importance of contextual features in RNA recognition, which likely enable targeting of distinct subsets of transcripts by different RBPs that recognize the same linear motif.
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•In vitro specificity of 78 human RNA binding proteins determined by deep sequencing•RBP motifs have low diversity, compositional complexity, and RNA structure potential•RBPs that bind similar motifs often differ in their sequence context preferences•Many favor specific “bipartite” motifs, flanking base composition, or RNA structures
Dominguez et al. describe in vitro binding specificities of 78 human RNA binding proteins (RBPs) to RNA sequences and structures. They find that many RBPs bind similar RNA motifs but differ in affinity for spaced “bipartite” motifs, flanking composition, and RNA structure, supporting the model that distinct motif occurrences are often discriminated based on sequence context.
How ornamentation enables a direct and immediate
encounter between viewers and art objects Based on
universal motifs, ornamentation occurs in many artistic traditions,
though it reaches its most ...expressive, tangible, and unique form in
the art of the Islamic world. The Mediation of Ornament
shares a veteran art historian's love for the sheer sensuality of
Islamic ornamentation, but also uses this art to show how ornament
serves as a consistent intermediary between viewers and artistic
works from all cultures and periods. Oleg Grabar analyzes early and
medieval Islamic objects, ranging from frontispieces in Yemen to
tilework in the Alhambra, and compares them to Western examples,
treating all pieces as testimony of the work, life, thought, and
emotion experienced in one society. The Mediation of
Ornament is essential reading for admirers of Islamic art and
anyone interested in the ways of perceiving and understanding the
arts more broadly.
During autophagy, vesicle dynamics and cargo recruitment are driven by numerous adaptors and receptors that become tethered to the phagophore through interactions with lipidated ATG8/LC3 decorating ...the expanding membrane. Most currently described ATG8-binding proteins exploit a well-defined ATG8-interacting motif (AIM, or LC3-interacting region LIR) that contacts a hydrophobic patch on ATG8 known as the LIR/AIM docking site (LDS). Here we describe a new class of ATG8 interactors that exploit ubiquitin-interacting motif (UIM)-like sequences for high-affinity binding to an alternative ATG8 interaction site. Assays with candidate UIM-containing proteins together with unbiased screens identified a large collection of UIM-based ATG8 interactors in plants, yeast, and humans. Analysis of a subset also harboring ubiquitin regulatory X (UBX) domains revealed a role for UIM-directed autophagy in clearing non-functional CDC48/p97 complexes, including some impaired in human disease. With this new class of adaptors and receptors, we greatly extend the reach of selective autophagy and identify new factors regulating autophagic vesicle dynamics.
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•A new binding site for autophagy adaptors and receptors was discovered on ATG8•This site engages UIM-like sequences rather than the canonical ATG8-interacting motif•UIM-type autophagy adaptors and receptors can be found in plants, yeast, and humans•UIM-containing UBX domain proteins mediate autophagic clearance of CDC48/p97
Across organisms, the key autophagy protein ATG8/LC3 binds a group of proteins on a site distinct from its classical interacting region, raising the possibility of dual binding interactions and identifying an array of previously unknown selective autophagic adaptors and receptors, including some involved in human disease.
This is a systematic study of the conceptual framework used by critics and scholars in their discussions of influence in art and literature. Göran Hermerén explores the key questions raised in ...scholarly debate on the topic: What is meant by "influence"? What methods can be used to settle disagreements about influence? What reasons could be used to support or reject statements about artistic and literary influence?
The book is based on descriptive analyses in which the author has tried to make explicit what is said or implied in a number of quotations from scholarly writings on art and literature. Throughout, the emphasis is on clarifying the assumptions on which the use of the concept of influence is based, thus describing the limitations and merits of this kind of comparative research for critics and scholars.
Originally published in 1975.
ThePrinceton Legacy Libraryuses the latest print-on-demand technology to again make available previously out-of-print books from the distinguished backlist of Princeton University Press. These paperback editions preserve the original texts of these important books while presenting them in durable paperback editions. The goal of the Princeton Legacy Library is to vastly increase access to the rich scholarly heritage found in the thousands of books published by Princeton University Press since its founding in 1905.
Focusing on songs by the troubadours and trouvères from
the twelfth to the fourteenth centuries,
Medieval Song from Aristotle to Opera
contends that song is not best analyzed as "words plus
music" ...but rather as a distinctive way of sounding words .
Rather than situating them in their immediate period, Sarah Kay
fruitfully listens for and traces crosscurrents between medieval
French and Occitan songs and both earlier poetry and much later
opera. Reflecting on a song's songlike quality-as, for example, the
sound of light in the dawn sky, as breathed by beasts, as sirenlike
in its perils-Kay reimagines the diversity of songs from this
period, which include inset lyrics in medieval French narratives
and the works of Guillaume de Machaut, as works that are as much
desired and imagined as they are actually sung and heard.
Kay understands song in terms of breath, the constellations, the
animal soul, and life itself. Her method also draws inspiration
from opera, especially those that inventively recreate medieval
song, arguing for a perspective on the manuscripts that transmit
medieval song as instances of multimedia, quasi-operatic
performances.
Medieval Song from Aristotle to Opera features a
companion website
(cornellpress.manifoldapp.org/projects/medieval-song) hosting
twenty-four audio or video recordings, realized by professional
musicians specializing in early music, of pieces discussed in the
book, together with performance scores, performance reflections,
and translations of all recorded texts. These audiovisual materials
represent an extension in practice of the research aims of the
book-to better understand the sung dimension of medieval song.
The eukaryotic linear motif (ELM http://elm.eu.org) resource is a hub for collecting, classifying and curating information about short linear motifs (SLiMs). For >10 years, this resource has provided ...the scientific community with a freely accessible guide to the biology and function of linear motifs. The current version of ELM contains ∼200 different motif classes with over 2400 experimentally validated instances manually curated from >2000 scientific publications. Furthermore, detailed information about motif-mediated interactions has been annotated and made available in standard exchange formats. Where appropriate, links are provided to resources such as switches.elm.eu.org and KEGG pathways.
Coronavirus disease 2019 (COVID-19), caused by the novel human coronavirus SARS-CoV-2, is currently a major threat to public health worldwide. The viral spike protein binds the host receptor ...angiotensin-converting enzyme 2 (ACE2) via the receptor-binding domain (RBD), and thus is believed to be a major target to block viral entry. Both SARS-CoV-2 and SARS-CoV share this mechanism. Here we functionally analyzed the key amino acid residues located within receptor binding motif of RBD that may interact with human ACE2 and available neutralizing antibodies. The in vivo experiments showed that immunization with either the SARS-CoV RBD or SARS-CoV-2 RBD was able to induce strong clade-specific neutralizing antibodies in mice; however, the cross-neutralizing activity was much weaker, indicating that there are distinct antigenic features in the RBDs of the two viruses. This finding was confirmed with the available neutralizing monoclonal antibodies against SARS-CoV or SARS-CoV-2. It is worth noting that a newly developed SARS-CoV-2 human antibody, HA001, was able to neutralize SARS-CoV-2, but failed to recognize SARS-CoV. Moreover, the potential epitope residues of HA001 were identified as A475 and F486 in the SARS-CoV-2 RBD, representing new binding sites for neutralizing antibodies. Overall, our study has revealed the presence of different key epitopes between SARS-CoV and SARS-CoV-2, which indicates the necessity to develop new prophylactic vaccine and antibody drugs for specific control of the COVID-19 pandemic although the available agents obtained from the SARS-CoV study are unneglectable.
Tau protein plays an important role in the biology of stress granules and in the stress response of neurons, but the nature of these biochemical interactions is not known. Here we show that the ...interaction of tau with RNA and the RNA binding protein TIA1 is sufficient to drive phase separation of tau at physiological concentrations, without the requirement for artificial crowding agents such as polyethylene glycol (PEG). We further show that phase separation of tau in the presence of RNA and TIA1 generates abundant tau oligomers. Prior studies indicate that recombinant tau readily forms oligomers and fibrils in vitro in the presence of polyanionic agents, including RNA, but the resulting tau aggregates are not particularly toxic. We discover that tau oligomers generated during copartitioning with TIA1 are significantly more toxic than tau aggregates generated by incubation with RNA alone or phase-separated tau complexes generated by incubation with artificial crowding agents. This pathway identifies a potentially important source for generation of toxic tau oligomers in tau-related neurodegenerative diseases. Our results also reveal a general principle that phase-separated RBP droplets provide a vehicle for coassortment of selected proteins. Tau selectively copartitions with TIA1 under physiological conditions, emphasizing the importance of TIA1 for tau biology. Other RBPs, such as G3BP1, are able to copartition with tau, but this happens only in the presence of crowding agents. This type of selective mixing might provide a basis through which membraneless organelles bring together functionally relevant proteins to promote particular biological activities.
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