RNA-targeting system

A non-naturally occurring or engineered vector system comprising one or more vectors comprising:

• a) a first regulatory element operably linked to a first polynucleotide sequence encoding an RNA-targeting guide RNA (Rt-gRNA), wherein said Rt-gRNA is designed to hybridize with a target RNA, wherein said Rt-gRNA comprises:
• (i) a small CRISPR/Cas system associated RNA (scaRNA) sequence, and
• (ii) a trans-activating CRISPR/Cas system RNA (tracrRNA) sequence, wherein said scaRNA and said tracrRNA are designed to at least partially hybridize to each other, and
• b) a second regulatory element operably linked to a second polynucleotide sequence encoding
• (i) a Francisella novicida Cas protein (FnCas) or ortholog, homolog, or fragment thereof comprising a Rec1 domain, Rec2 domain, HNH domain, and PAM Interacting (PI) domain, and
• (ii) one or more heterologous functional domains positioned at one or more sites in FnCas that are analogous to amino acid positions 534-676 corresponding to a wild type Streptococcus pyogenes Cas9 (SpCas9) Rec1 domain
• wherein the Rt-gRNA is capable of forming an RNA-targeting complex with the FnCas and of directing sequence-specific binding of the RNA-targeting complex to the target RNA,
• wherein each of the one or more heterologous functional domains comprise one or more of the following activities:
• methylase activity, demethylase activity, translation activation activity, translation repression activity, histone modification activity, RNA cleavage activity, or DNA cleavage activity, and
• wherein components (a) and (b) are located on the same or different vectors of the system and wherein the Rt-gRNA and said FnCas protein do not naturally occur together.