Methods and compositions related to the use of Mobile Element Insertions and their adjacent genomic sequences. Methods using MEIs as markers for cellular proliferation, as targets for pharmaceuticals, as markers for tissue fingerprinting and in related methods and compositions are disclosed herein. Methods and compositions relate to the detection, treatment and ongoing monitoring of cell proliferation events, cancer, and deleterious effects of mobile elements in aging, and to the selection, use and monitoring of the success of treatment regimens to address these conditions.

A DNA methyltransferase is derived from Deinococcus radiodurans and has a typical conservative structural domain of DNA methyltransferase. The DNA methyltransferase includes: an AdoMet binding region containing a “FxGxG” conservative sequence, a target sequence recognition region and a catalytic region containing a “TSPPY” conservative sequence sequentially from N-terminal to C-terminal; and belongs to α-type DNA methyltransferase category. The recognized substrate DNA conservative sequence is 5′-CCGCGG-3′, a methylation modified position is N4 site of second cytosine to generate a 4mC type modified base, and an optimum temperature for methylated reaction is in a range of 25-37° C. The DNA methyltransferase can specific-recognize the conservative motif of “CCGCGG” and methylate the N4 site of the second cytosine to produce the 4mC modified base, which is a N4-Cytosine DNA methyltransferase.

Methods and kits for detecting the presence of at least one target DNA sequence with or without a modification in a DNA molecule are provided.

The disclosure provides programmable methylation “writers” and demethylation “erasers” for editing the methylation state of RNA targets, e.g., an RNA transcriptome. In particular, the disclosure provides RNA methylation editor polynucleotide contracts and vectors comprising (i) an RNA programmable RNA binding domain (RNApRNAbd); and (ii) an effector domain, wherein the effector domain is capable of adding or removing a methyl group in an RNA. The disclosed RNA methylation editor constructs are capable of achieving limited off-target modifications in RNA molecules. Further, the disclosure provides methods for making and using the programmable methylation editors to modifying the methylation state of RNA. The disclosure further provides complexes comprising a methylation writer protein and a guide RNA molecule and complexes comprising a demethylation eraser protein and a guide RNA molecule. The disclosure further provides pharmaceutical compositions and cells comprising the disclosed fusion proteins and complexes.

Provided herein are methods for modulating the psilocybin biosynthesis pathway in fungi or other organisms. Also provided are genetically modified fungi and organisms with induced and/or increased expression of psilocybin and psilocin and psilocybin and/or psilocin compositions generated by the provided methods.

The purpose of the present invention is to provide an organism having an ergothioneine productivity that is capable of easily producing ergothioneine within a short period of time at a high yield, as compared with a conventional technology, and, therefore, enables ergothioneine production on an industrial scale. This purpose can be achieved by a transformed fungus into which a gene encoding enzyme (1) or genes encoding enzymes (1) and (2) have been inserted and in which the inserted gene(s) are overexpressed. (1) an enzyme catalyzing a reaction of synthesizing hercynyl cysteine sulfoxide from histidine and cysteine in the presence of S-adenosyl methionine, iron (II) and oxygen. (2) An enzyme catalyzing a reaction of synthesizing ergothioneine from hercynyl cysteine sulfoxide using pyridoxal 5′-phosphate as a coenzyme.

A transkingdom platform for the delivery of therapeutic nucleic acids to epithelial tissues where the nucleic acids are designed to have enhanced stability. The platform offers numerous improvements to prior delivery platforms including expression of the double-stranded RNA binding domain (dsRBD) domains of TAR RNA binding protein (TRBP), knockout of RNase R activity in the bacterial delivery vehicle, and expression of the methyltransferase gene, HEN1, for simultaneous packaging with a therapeutic nucleic acid delivery vehicle.

The purpose of the present invention is to provide an organism having an ergothioneine productivity that is capable of easily producing ergothioneine within a short period of time at a high yield, as compared with a conventional technology, and, therefore, enables ergothioneine production on an industrial scale. This purpose can be achieved by a transformed fungus into which a gene encoding enzyme (1) or genes encoding enzymes (1) and (2) have been inserted and in which the inserted gene(s) are overexpressed. (1) an enzyme catalyzing a reaction of synthesizing hercynyl cysteine sulfoxide from histidine and cysteine in the presence of S-adenosyl methionine, iron (II) and oxygen. (2) An enzyme catalyzing a reaction of synthesizing ergothioneine from hercynyl cysteine sulfoxide using pyridoxal 5′-phosphate as a coenzyme.

Methods and constructs for RNA-guided targeting of heterologous functional domains such as transcriptional activators to specific genomic loci.

The invention describes the discovery and novel application of a bacterial ubiquitin transferase (Cap2). Specifically, the invention describes the novel activity of the enzyme Cap2 which is capable of creating a specific fusion between two proteins implementing a standalone catalytic mechanism to create the fusion.