Using in vitro assays, which recapitulate Argonaute-specific loop loading from synthetic pre-miRNAs and even single-stranded oligoribonucleotides corresponding to miRNA loops, we reveal that the loop-loading mechanism is distinct from duplex loading. We also show that miRNA loops loaded into the miRNA effector AGO1 are subject to 39 resection, and structure-function analyses indicate selectivity of loop loading. Finally, we demonstrate that select miRNA loops in mammals are similarly loaded into Argonaute complexes and direct target STA-9090 in vivo repression. Altogether, we reveal a conserved mechanism that yields functional RNAs from miRNA loop regions, broadening the repertoire

of Argonaute-dependent regulatory RNAs and providing evidence selleck screening library for functionality of endogenous ssRNA species.”
“Most anaplastic large cell lymphomas (ALCL) express oncogenic fusion proteins derived

from chromosomal translocations or inversions of the anaplastic lymphoma kinase (ALK) gene. Frequently ALCL carry the t(2;5) translocation, which fuses the ALK gene to the nucleophosmin (NPM1) gene. The transforming activity mediated by NPM-ALK fusion induces different pathways that control proliferation and survival of lymphoma cells. Grb2 is an adaptor protein thought to play an important role in ALK-mediated transformation, but its interaction with NPM-ALK, as well as its function in regulating ALCL signaling pathways and cell growth, has never been elucidated. Here we show that active NPM-ALK, but not a kinase-dead mutant, bound and induced Grb2 phosphorylation in tyrosine 160. An intact SH3 domain at the C terminus of Grb2 was required for Tyr(160) phosphorylation. Furthermore, Grb2 did not bind to a single region but rather to different regions of NPM-ALK, mainly Tyr(152-156), Tyr(567), and a proline-rich region, Pro(415-417). Finally, shRNA knockdown experiments ACY-241 showed that Grb2 regulates primarily the NPM-ALK-mediated phosphorylation of SHP2 and plays a key role in ALCL cell growth.”
“Background:

Reestablishment of apex predators influences the availability and distribution of biomass for scavengers and can therefore be an important agent for structuring species communities. We studied how the re-colonization of the Scandinavian Peninsula by wolves (Canis lupus) affected the amount and temporal variation in use of moose (Alces alces) carcasses.\n\nMethodology/Principal Findings: We compared the availability of biomass from remains at wolf kills with those killed by hunters, vehicle collisions and natural death. Movement-triggered cameras monitored patterns of use on wolf kills and remains from hunter harvest by scavengers (n = 15 276) in relation to time of year, available carcass biomass, time since the death of the moose and presence of wolves. Remains from hunter harvest were the largest food source for scavengers both within wolf territories (57%) and in areas without wolves (81%).