Encephalopathy in sheep was at first described in Ireland in 1732 and was called scrapie. Ancient DNA in archaeogenetics represents an effective method to evaluate the ancestral pedigree of living animals and track ev...Encephalopathy in sheep was at first described in Ireland in 1732 and was called scrapie. Ancient DNA in archaeogenetics represents an effective method to evaluate the ancestral pedigree of living animals and track evolutionary changes occurred between the past and the present day. Since several point mutations are today widely described in modern scrapie, no data about both sequence and frequency are still available for the prion protein (PrP) gene in ancient breeds. In order to evaluate whether the haplotypes distribution in ancient sheep differed from those of the modern population we evaluated polymorphism at four well know codons of the Prp Open Reading Frame. In the present work, we collected 37 medieval sheep bone remains found at the Calathamet (n = 11), Palazzo Bonagia (n = 12) and Palazzo Steri (n = 14) Sicilians archeological sites and dated back between 9th - 15th century. Single nucleotide polymorphisms (SNPs) at codons 136, 141, 154 and 171 of the prion protein (PrP) were investigated using cycle sequencing. Sequenom Mass ARRAYiPLEX platform confirmed the results for 5 individuals out of 37. Cycle sequencing showed at all samples the AA136LL141RR154QQ171 (hereafter ALRQ/ALRQ) genotype except at 2 individuals showing the very susceptible genotype VLRQ/VLRQ (n = 1) and the resistant (ALRR/ ALRR) (n = 1) respectively. Supported by a high incidence of susceptible genotype to prion infection we concluded that presumably scrapie was already widespread enough in the medieval Sicily. Moreover, we described conceivable scenarios that could have underlain evolutionary changes in the medieval sheep population.展开更多
Heterogeneous nuclear ribonucleoproteins（hn RNPs） belong to the RNA-binding proteins family. They are involved in processing heterogeneous nuclear RNAs（hn RNAs） into mature m RNAs. These proteins participate in ev...Heterogeneous nuclear ribonucleoproteins（hn RNPs） belong to the RNA-binding proteins family. They are involved in processing heterogeneous nuclear RNAs（hn RNAs） into mature m RNAs. These proteins participate in every step of m RNA cycle, such as m RNA export, localization, translation, stability and alternative splicing. At least 14 major hn RNPs, which have structural and functional homologues in mammals, are expressed in Drosophila melanogaster. Until now, six of these hn RNPs are known to be nucleus-localized and associated with the long non-coding RNA（lnc RNA） heat shock responsive u（hsru）in the omega speckle compartments（u-speckles）. The chromatin remodeler ISWI is the catalytic subunit of several ATP-dependent chromatin-remodeling complexes, and it is an essential factor for organization of u-speckles. Indeed, in ISWI null mutant, severe defects in u-speckles structure are detectable. Here, we clarify the role of ISWI in the hn RNPs-hsru interaction. Moreover, we describe how ISWI by its remodeling activity, controls hsru and hn RNPs engagement in u-speckles. Finally, we demonstrate that the sequestration of hn RNPs in u-speckles nuclear compartment is a fundamental event in gene expression control and represents a key step in the regulation of several pathways.展开更多
文摘Encephalopathy in sheep was at first described in Ireland in 1732 and was called scrapie. Ancient DNA in archaeogenetics represents an effective method to evaluate the ancestral pedigree of living animals and track evolutionary changes occurred between the past and the present day. Since several point mutations are today widely described in modern scrapie, no data about both sequence and frequency are still available for the prion protein (PrP) gene in ancient breeds. In order to evaluate whether the haplotypes distribution in ancient sheep differed from those of the modern population we evaluated polymorphism at four well know codons of the Prp Open Reading Frame. In the present work, we collected 37 medieval sheep bone remains found at the Calathamet (n = 11), Palazzo Bonagia (n = 12) and Palazzo Steri (n = 14) Sicilians archeological sites and dated back between 9th - 15th century. Single nucleotide polymorphisms (SNPs) at codons 136, 141, 154 and 171 of the prion protein (PrP) were investigated using cycle sequencing. Sequenom Mass ARRAYiPLEX platform confirmed the results for 5 individuals out of 37. Cycle sequencing showed at all samples the AA136LL141RR154QQ171 (hereafter ALRQ/ALRQ) genotype except at 2 individuals showing the very susceptible genotype VLRQ/VLRQ (n = 1) and the resistant (ALRR/ ALRR) (n = 1) respectively. Supported by a high incidence of susceptible genotype to prion infection we concluded that presumably scrapie was already widespread enough in the medieval Sicily. Moreover, we described conceivable scenarios that could have underlain evolutionary changes in the medieval sheep population.
基金supported by an Associazione Italiana Ricerca sul Cancro (AIRC) (MFAG-12779) fellowshipsupported by My First Airc Grant (MFAG) number 12779 from AIRC to M.C.O
文摘Heterogeneous nuclear ribonucleoproteins（hn RNPs） belong to the RNA-binding proteins family. They are involved in processing heterogeneous nuclear RNAs（hn RNAs） into mature m RNAs. These proteins participate in every step of m RNA cycle, such as m RNA export, localization, translation, stability and alternative splicing. At least 14 major hn RNPs, which have structural and functional homologues in mammals, are expressed in Drosophila melanogaster. Until now, six of these hn RNPs are known to be nucleus-localized and associated with the long non-coding RNA（lnc RNA） heat shock responsive u（hsru）in the omega speckle compartments（u-speckles）. The chromatin remodeler ISWI is the catalytic subunit of several ATP-dependent chromatin-remodeling complexes, and it is an essential factor for organization of u-speckles. Indeed, in ISWI null mutant, severe defects in u-speckles structure are detectable. Here, we clarify the role of ISWI in the hn RNPs-hsru interaction. Moreover, we describe how ISWI by its remodeling activity, controls hsru and hn RNPs engagement in u-speckles. Finally, we demonstrate that the sequestration of hn RNPs in u-speckles nuclear compartment is a fundamental event in gene expression control and represents a key step in the regulation of several pathways.
