Abstract: By modifying nucleotides from either or both the stem and loop of precursor-miRNA, greater specificity is achieved as to the mRNAs targeted. The improved efficiency in target regulation can be either mediated by direct base-pairings between targets and precursor miRNAs or indirectly by energy constraints on the availability of such base-pairings. It is found that pri- and pre-miRNA are active in the absence of functional mature miRNA, so pri- or pre-miRNA or truncated portion thereof, but not as mature miRNA, can be used as RNAi agents by themselves. Furthermore, besides the seed sequence of the stem of the pre-miRNA and 3?-extensions thereof to provide greater complementarity to the target mRNA, nucleotides in the loop can affect the activity and specificity of the precursor-miRNA and the processing and binding to target mRNA.

Abstract: MicroRNAs (miRNAs) are a diverse and abundant class of ˜22-nucleotide (nt) endogenous regulatory RNAs that play a variety of roles in animal cells by controlling gene expression at the posttranscriptional level. Increased miR-181a expression in mature T cells is shown to cause a marked increase in T cell activation and augments T cell sensitivity to peptide antigens. Moreover, T cell blasts with higher miR-181a expression become reactive to antagonists. The effects of miR-181a on antigen discrimination are in part achieved by dampening the expression of multiple negative regulators in the T cell receptor (TCR) signaling pathway, including PTPN22 and the dual specificity phosphatases DUSP5 and DUSP6. This results in a reduction in the TCR signaling threshold, thus quantitatively and qualitatively enhancing T cell sensitivity to antigens.

Abstract: The ability of miR-181a to support active signaling between Notch and pre-TCR pathways by coordinately dampening negative regulators of these pathways allows the use of miR-181a as a therapeutic target for T-ALL.

Abstract: By employing essential nucleotides from both the stem and loop of precursor-miRNA, greater specificity is achieved as to the mRNAs that are repressed. It is found that besides the seed sequence of the stem of the pre-miRNA, nucleotides in the loop affect the activity and specificity of the cursor- and the processing and binding to target mRNA. By using both sequences in the natural pre-miRNA or modified mimetics, one can screen for cellular miRNA expression, modulate cell properties with greater specificity and investigate cellular activity as to phenotype and response to external stimuli in the presence and absence of target protein expression.

Abstract: MicroRNAs (miRNAs) are a diverse and abundant class of ˜22-nucleotide (nt) endogenous regulatory RNAs that play a variety of roles in animal cells by controlling gene expression at the posttranscriptional level. Increased miR-181a expression in mature T cells is shown to cause a marked increase in T cell activation and augments T cell sensitivity to peptide antigens. Moreover, T cell blasts with higher miR-181a expression become reactive to antagonists. The effects of miR-181a on antigen discrimination are in part achieved by dampening the expression of multiple negative regulators in the T cell receptor (TCR) signaling pathway, including PTPN22 and the dual specificity phosphatases DUSP5 and DUSP6. This results in a reduction in the TCR signaling threshold, thus quantitatively and qualitatively enhancing T cell sensitivity to antigens.

Abstract: The invention relates to microRNAs, methods of producing microRNAs and methods for using microRNAs.

Abstract: Methods of marking pluripotent cells, such as stem cells, particularly hematopoietic stem cells; methods of detecting/identifying, enriching, selecting and monitoring pluripotent cells (stem cells); DNA constructs useful in the methods, stem cells, such as hematopoietic stem cells, identified by the method, as well as lineage-specific cells identified by the method; and uses for the cells are subjects of this invention.