Identifying the sequence specificities of circRNA-binding proteins based on a capsule network architecture

Background Circular RNAs (circRNAs) are widely expressed in cells and tissues and are involved in biological processes and human diseases. Recent studies have demonstrated that circRNAs can interact with RNA-binding proteins (RBPs), which is considered an important aspect for investigating the function of circRNAs. Results In this study, we design a slight variant of the capsule network, called circRB, to identify the sequence specificities of circRNAs binding to RBPs. In this model, the sequence features of circRNAs are extracted by convolution operations, and then, two dynamic routing algorithms in a capsule network are employed to discriminate between different binding sites by analysing the convolution features of binding sites. The experimental results show that the circRB method outperforms the existing computational methods. Afterwards, the trained models are applied to detect the sequence motifs on the seven circRNA-RBP bound sequence datasets and matched to known human RNA motifs. Some motifs on circular RNAs overlap with those on linear RNAs. Finally, we also predict binding sites on the reported full-length sequences of circRNAs interacting with RBPs, attempting to assist current studies. We hope that our model will contribute to better understanding the mechanisms of the interactions between RBPs and circRNAs. Conclusion In view of the poor studies about the sequence specificities of circRNA-binding proteins, we designed a classification framework called circRB based on the capsule network. The results show that the circRB method is an effective method, and it achieves higher prediction accuracy than other methods.

BEN-solo factors partition active chromatin to ensure proper gene activation in Drosophila

The Drosophila genome encodes three BEN-solo proteins including Insensitive (Insv), Elba1 and Elba2 that possess activities in transcriptional repression and chromatin insulation. A fourth protein—Elba3—bridges Elba1 and Elba2 to form an ELBA complex. Here, we report comprehensive investigation of these proteins in Drosophila embryos. We assess common and distinct binding sites for Insv and ELBA and their genetic interdependencies. While Elba1 and Elba2 binding generally requires the ELBA complex, Elba3 can associate with chromatin independently of Elba1 and Elba2. We further demonstrate that ELBA collaborates with other insulators to regulate developmental patterning. Finally, we find that adjacent gene pairs separated by an ELBA bound sequence become less differentially expressed in ELBA mutants. Transgenic reporters confirm the insulating activity of ELBA- and Insv-bound sites. These findings define ELBA and Insv as general insulator proteins in Drosophila and demonstrate the functional importance of insulators to partition transcription units.

Investigation of collision-induced dissociation products and structures of gas-phase [M·GlyGlyHis-H]+ (M = Fe, Ni, Cu, and Zn) complexes

Collision-induced dissociation is carried out for electrosprayed [Fe·GlyGlyHis-H]+, [Ni·GlyGlyHis-H]+, [Cu·GlyGlyHis-H]+, and [Zn·GlyGlyHis-H]+ complexes. [Fe·GlyGlyHis-H]+, [Ni·GlyGlyHis-H]+, and [Zn·GlyGlyHis-H]+ yield metal-bound peptide sequence ions and dehydrated ions as primary products, whereas [Cu·GlyGlyHis-H]+ generates a more extensive series of metal-bound sequence ions and a product arising from the unusual loss of a formaldehyde moiety; dehydration is significantly suppressed for this complex. Density functional theory calculations show that the copper ion-deprotonated peptide binding energy is substantially higher than those in other complexes, suggesting that there is a correlation between ion–ligand binding energy and their fragmentation behavior.

Abstract 217: Quaking Post-Transcriptionally Guides Monocyte Adhesion and Differentiation into the Pro-Inflammatory Macrophage

A hallmark of inflammatory diseases is the excessive recruitment and influx of monocytes to sites of tissue damage and their ensuing differentiation into macrophages. Numerous stimuli are known to induce new transcription necessary for macrophage identity, but post-transcriptional control of human macrophage differentiation is less well understood. Here, we detail our discovery that levels of the RNA-binding protein Quaking (QKI) are low in monocytes of early atherosclerotic lesions, but abundant in macrophages of advanced plaques. Specific depletion of QKI protein impaired monocyte adhesion, migration and differentiation into macrophages, and lesion formation. RNA-seq and microarray analysis of human monocyte and macrophage transcriptomes, including those of a unique QKI haploinsufficient patient, reveal developmental changes in RNA levels and alternative splicing of RNA transcripts enriched in QKI-bound sequence elements. The importance of these transcripts and requirement for QKI during differentiation illustrates a central role for QKI in post-transcriptionally guiding macrophage identity and function. These studies implicate QKI as a novel target for therapeutic intervention in inflammatory diseases.

A hierarchical study of neutralization in Kasem

The grammar of Kasem is being analysed in terms of a hierarchical model (cf. Halliday, 1961; Bendor-Samuel, 1963), the (ascending) levels of relevance to this paper being word, phrase, clause, string, and sentence. (The ‘string’ is the unit which functions in the sentence and consists of a tightly bound sequence of clauses, the non-initial clauses operating under extensive restrictions with respect to their structure. This type of syntactic unit appears to be characteristic of many Gur languages and is often referred to as a ‘series’ or ‘serial construction’. For a recent discussion in some detail of this unit, under the term ‘clause clusters’, see Pike, 1966: 55–78.) At the word level in this hierarchy, a system of categories can be set up to account for the form of every verb word, i.e. so that every verb word can be completely ‘parsed’ or described in terms of these categories. But one of the characteristic features of this system of categories is that there is extensive neutralization between the categories. The question, then, that this paper seeks to discuss is this: are the ambiguities inherent in the verb word resolved within the language as a whole? An answer is here presented which seeks to relate the resolution of the ambiguities to the different levels of the grammatical hierarchy, as set up.