@article {68408,
	title = {Structure of the OMEGA nickase IsrB in complex with ωRNA and target DNA.},
	journal = {Nature},
	volume = {610},
	year = {2022},
	month = {2022 Oct 12},
	pages = {575-581},
	abstract = {<p>RNA-guided systems, such as CRISPR-Cas, combine programmable substrate recognition with enzymatic function, a combination that has been used advantageously to develop powerful molecular technologies. Structural studies of these systems have illuminated how the RNA and protein jointly recognize and cleave their substrates, guiding rational engineering for further technology development. Recent work identified a new class of RNA-guided systems, termed OMEGA, which include IscB, the likely ancestor of Cas9, and the nickase IsrB, a homologue of IscB lacking the HNH nuclease domain. IsrB consists of only around 350 amino acids, but its small size is counterbalanced by a relatively large RNA guide (roughly 300-nt ωRNA). Here, we report the cryogenic-electron microscopy structure of Desulfovirgula thermocuniculi IsrB (DtIsrB) in complex with its cognate ωRNA and a target DNA. We find the overall structure of the IsrB protein shares a common scaffold with Cas9. In contrast to Cas9, however, which uses a recognition (REC) lobe to facilitate target selection, IsrB relies on its ωRNA, part of which forms an intricate ternary structure positioned analogously to REC. Structural analyses of IsrB and its ωRNA as well as comparisons to other RNA-guided systems highlight the functional interplay between protein and RNA, advancing our understanding of the biology and evolution of these diverse systems.</p>
},
	keywords = {CRISPR-Associated Proteins, CRISPR-Cas Systems, Cryoelectron Microscopy, Deoxyribonuclease I, DNA, RNA, Guide},
	issn = {1476-4687},
	doi = {10.1038/s41586-022-05324-6},
	author = {Hirano, Seiichi and Kappel, Kalli and Altae-Tran, Han and Faure, Guilhem and Wilkinson, Max E and Kannan, Soumya and Demircioglu, F Esra and Yan, Rui and Shiozaki, Momoko and Yu, Zhiheng and Makarova, Kira S and Koonin, Eugene V and Macrae, Rhiannon K and Zhang, Feng}
}
@article {1205,
	title = {Manipulation of an innate escape response in Drosophila: photoexcitation of acj6 neurons induces the escape response.},
	journal = {PLoS One},
	volume = {4},
	year = {2009},
	month = {2009 Apr 2},
	pages = {e5100},
	abstract = {<p>BACKGROUND: The genetic analysis of behavior in Drosophila melanogaster has linked genes controlling neuronal connectivity and physiology to specific neuronal circuits underlying a variety of innate behaviors. We investigated the circuitry underlying the adult startle response, using photoexcitation of neurons that produce the abnormal chemosensory jump 6 (acj6) transcription factor. This transcription factor has previously been shown to play a role in neuronal pathfinding and neurotransmitter modality, but the role of acj6 neurons in the adult startle response was largely unknown. PRINCIPAL FINDINGS: We show that the activity of these neurons is necessary for a wild-type startle response and that excitation is sufficient to generate a synthetic escape response. Further, we show that this synthetic response is still sensitive to the dose of acj6 suggesting that that acj6 mutation alters neuronal activity as well as connectivity and neurotransmitter production. RESULTS/SIGNIFICANCE: These results extend the understanding of the role of acj6 and of the adult startle response in general. They also demonstrate the usefulness of activity-dependent characterization of neuronal circuits underlying innate behaviors in Drosophila, and the utility of integrating genetic analysis into modern circuit analysis techniques.</p>
},
	keywords = {Animal, Animals, Base Sequence, Behavior, DNA Primers, Drosophila melanogaster, Genetically Modified, Neurons, Startle Reaction},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0005100},
	author = {Zimmermann, Gregor and Wang, Li-Ping and Vaughan, Alexander G and Manoli, Devanand S and Zhang, Feng and Deisseroth, Karl and Baker, Bruce S and Scott, Matthew P}
}
