The increasing diversity of functions attributed to the SAFB family of RNA/DNA binding proteins

RNA-binding proteins play a central role in cellular metabolism by orchestrating the complex interactions of coding, structural and regulatory RNA species. The SAFB (scaffold attachment factor B) proteins (SAFB1, SAFB2 and SAFB-like transcriptional modulator, SLTM), which are highly conserved evolutionarily, were first identified on the basis of their ability to bind scaffold attachment region DNA elements, but attention has subsequently shifted to their RNA-binding and protein–protein interactions. Initial studies identified the involvement of these proteins in the cellular stress response and other aspects of gene regulation. More recently, the multifunctional capabilities of SAFB proteins have shown that they play crucial roles in DNA repair, processing of mRNA and regulatory RNA, as well as in interaction with chromatin-modifying complexes. With the advent of new techniques for identifying RNA-binding sites, enumeration of individual RNA targets has now begun. This review aims to summarise what is currently known about the functions of SAFB proteins.</jats:p

iCLIP identifies novel roles for SAFB1 in regulating RNA processing and neuronal function

BACKGROUND: SAFB1 is a RNA binding protein implicated in the regulation of multiple cellular processes such as the regulation of transcription, stress response, DNA repair and RNA processing. To gain further insight into SAFB1 function we used iCLIP and mapped its interaction with RNA on a genome wide level. RESULTS: iCLIP analysis found SAFB1 binding was enriched, specifically in exons, ncRNAs, 3’ and 5’ untranslated regions. SAFB1 was found to recognise a purine-rich GAAGA motif with the highest frequency and it is therefore likely to bind core AGA, GAA, or AAG motifs. Confirmatory RT-PCR experiments showed that the expression of coding and non-coding genes with SAFB1 cross-link sites was altered by SAFB1 knockdown. For example, we found that the isoform-specific expression of neural cell adhesion molecule (NCAM1) and ASTN2 was influenced by SAFB1 and that the processing of miR-19a from the miR-17-92 cluster was regulated by SAFB1. These data suggest SAFB1 may influence alternative splicing and, using an NCAM1 minigene, we showed that SAFB1 knockdown altered the expression of two of the three NCAM1 alternative spliced isoforms. However, when the AGA, GAA, and AAG motifs were mutated, SAFB1 knockdown no longer mediated a decrease in the NCAM1 9–10 alternative spliced form. To further investigate the association of SAFB1 with splicing we used exon array analysis and found SAFB1 knockdown mediated the statistically significant up- and downregulation of alternative exons. Further analysis using RNAmotifs to investigate the frequency of association between the motif pairs (AGA followed by AGA, GAA or AAG) and alternative spliced exons found there was a highly significant correlation with downregulated exons. Together, our data suggest SAFB1 will play an important physiological role in the central nervous system regulating synaptic function. We found that SAFB1 regulates dendritic spine density in hippocampal neurons and hence provide empirical evidence supporting this conclusion. CONCLUSIONS: iCLIP showed that SAFB1 has previously uncharacterised specific RNA binding properties that help coordinate the isoform-specific expression of coding and non-coding genes. These genes regulate splicing, axonal and synaptic function, and are associated with neuropsychiatric disease, suggesting that SAFB1 is an important regulator of key neuronal processes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12915-015-0220-7) contains supplementary material, which is available to authorized users

Effect of work programme in extension of time entitlement

The aim of this research is to know how a construction work programme can be a tool in reducing disputes which relate to extension of time (eot). Extension of time entitlement is only granted to the successful claimant (contractor) who had fulfill certain conditions in the application and one of the condition is the claimant had successfully proved that the delay happened was not by his fault, it is either caused by employer or was one of the neutral events. Therefore it is important for the contractor to have sufficient records and documents about a project’s progress so that he is able to prove the caused of the delay occurred. Unfortunately, most of the contractors failed to do so because they are more focus to the work on site rather than doing the management and documentation work. It is believed then that by having a proper method of work progamme and updated progress of work can be so helpful in resolving the dispute, even the preparation of it are not required in any of local standard form of contract. This research are based on literature information about work programme and it will supported by referring to court case where had considered work programme as an important document in judgment. Even there are no specifications of method in preparing a work programme but there are some important elements in the work programme which may contribute to its purpose. Besides having credits in resolving disputes, there are still weak points in the work programme application which have to be studied and improved. It is found that it is good to have work programme requirement in document contract for the better future and quality of the industr

Spinal Cord Injury: Pathophysiology, Multimolecular Interactions, and Underlying Recovery Mechanisms

Spinal cord injury (SCI) is a destructive neurological and pathological state that causes major motor, sensory and autonomic dysfunctions. Its pathophysiology comprises acute and chronic phases and incorporates a cascade of destructive events such as ischemia, oxidative stress, inflammatory events, apoptotic pathways and locomotor dysfunctions. Many therapeutic strategies have been proposed to overcome neurodegenerative events and reduce secondary neuronal damage. Efforts have also been devoted in developing neuroprotective and neuro-regenerative therapies that promote neuronal recovery and outcome. Although varying degrees of success have been achieved, curative accomplishment is still elusive probably due to the complex healing and protective mechanisms involved. Thus, current understanding in this area must be assessed to formulate appropriate treatment modalities to improve SCI recovery. This review aims to promote the understanding of SCI pathophysiology, interrelated or interlinked multimolecular interactions and various methods of neuronal recovery i.e., neuroprotective, immunomodulatory and neuro-regenerative pathways and relevant approaches

Towards semi-supervised learning of semantic spatial concepts for mobile robots

The ability of building robust semantic space representations of environments is crucial for the development of truly autonomous robots. This task, inherently connected with cognition, is traditionally achieved by training the robot with a supervised learning phase. We argue that the design of robust and autonomous systems would greatly benefit from adopting a semi-supervised online learning approach. Indeed, the support of open-ended, lifelong learning is fundamental in order to cope with the dazzling variability of the real world, and online learning provides precisely this kind of ability. Here we focus on the robot place recognition problem, and we present an online place classification algorithm that is able to detect gap in its own knowledge based on a confidence measure. For every incoming new image frame, the method is able to decide if (a) it is a known room with a familiar appearance, (b) it is a known room with a challenging appearance, or (c) it is a new, unknown room. Experiments on ImageCLEF database and a subset of the challenging COLD database show the promise of our approach