Search

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a highly conserved family of RNA-binding proteins able to associate with nascent RNAs in order to support their localization, maturation and translation. Research over this last decade has remarked the importance of gene regulatory processes at post-transcriptional level, highlighting the emerging roles of hnRNPs in several essential biological events. Indeed, hnRNPs are key factors in regulating gene expression, thus, having a number of roles in many biological pathways. Moreover, failure of the activities catalysed by hnRNPs affects various biological processes and may underlie several human diseases including cancer, diabetes and neurodegenerative syndromes. In this review, we summarize some of hnRNPs' roles in the model organism Drosophila melanogaster, particularly focusing on their participation in all aspects of post-transcriptional regulation as well as their conserved role and involvement in the aetiology of human pathologies.

The packaging of DNA into chromatin facilitates the storage of the genetic information within the nucleus but prevents the access to the underlying sequences. The evolutionarily conserved ISWI family of ATP-dependent chromatin remodelling complexes provide one of the regulatory mechanisms that eukaryotic cells have evolved to induce structural changes to chromatin. All ISWI-containing complexes use the energy derived from ATP hydrolysis in order to rearrange nucleosomes on chromatin to carry specific nuclear reactions. The combination of associated proteins with the ATPase subunit as well as specific histone modifications specialize the nuclear function of each ISWI-containing complex. Here we review the many way through which ISWI enzymatic activity can be modulated and regulated in the nucleus of eukaryotic cells.

The evolutionarily conserved ATP-dependent nucleosome remodelling factor ISWI can space nucleosomes affecting a variety of nuclear processes. In Drosophila, loss of ISWI leads to global transcriptional defects and to dramatic alterations in higher-order chromatin structure, especially on the male X chromosome. In order to understand if chromatin condensation and gene expression defects, observed in ISWI mutants, are directly correlated with ISWI nucleosome spacing activity, we conducted a genome-wide survey of ISWI binding and nucleosome positioning in wild-type and ISWI mutant chromatin. Our analysis revealed that ISWI binds both genic and intergenic regions. Remarkably, we found that ISWI binds genes near their promoters causing specific alterations in nucleosome positioning at the level of the Transcription Start Site, providing an important insights in understanding ISWI role in higher eukaryote transcriptional regulation. Interestingly, differences in nucleosome spacing, between wild-type and ISWI mutant chromatin, tend to accumulate on the X chromosome for all ISWI-bound genes analysed. Our study shows how in higher eukaryotes the activity of the evolutionarily conserved nucleosome remodelling factor ISWI regulates gene expression and chromosome organization genome-wide.

In the quest for a mathematical measure able to capture and shed light on the dual notions of information and complexity in biosequences, Hazen et al. have introduced the notion of Functional Information (FI for short). It is also the result of earlier considerations and findings by Szostak and Carothers et al. Based on the experiments by Charoters et al., regarding FI in RNA binding activities, we decided to study the relation existing between FI and classic measures of complexity applied on protein-DNA interactions on a genome-wide scale. Using classic complexity measures, i.e, Shannon entropy and Kolmogorov Complexity as both estimated by data compression, we found that FI applied to protein-DNA interactions is genuinely different from them. Such a fact, together with the non-triviality of the biological function considered, contributes to the establishment of FI as a novel and useful measure of biocomplexity. Remarkably, we also found a relationship, on a genome-wide scale, between the redundancy of a genomic region and its ability to interact with a protein. This latter finding justifies even more some principles for the design of motif discovery algorithms. Finally, our experiments bring to light methodological limitations of Linguistic Complexity measures, i.e., a class of measures that is a function of the vocabulary richness of a sequence. Indeed, due to the technology and associated statistical preprocessing procedures used to conduct our studies, i.e., genome-wide ChIP-chip experiments, that class of measures cannot give any statistically significant indication about complexity and function. A serious limitation due to the widespread use of the technology. References J.M. Carothers, S.C. Oestreich, J.H. Davis, and J.W. Szostack. Informational complexity and functional activity of RNA structures. J. AM. CHEM. SOC., 126 (2004), pp. 5130-5137. R.M. Hazen, P.L. Griffin, J.M. Carothers, and J.W. Szostak. Functional Information and the emergence of biocomplexity. Proc. of Nat. Acad. Sci, 104 (2007), pp. 8574-8581. J.W. Szostak. Functional Information: molecular messages, Nature, 423 (2003).