MicroRNases and the Regulated Degradation of Mature Animal miRNAs.

microRNAs (miRNAs) are small noncoding RNAs that regulate numerous target mRNAs through an antisense mechanism. Initially thought to be very stable with half-lives on the orderof days, mature miRNAs haverecently been shown to be subject to degradation by 'microRNases' (miRNases) in plants (the small RNA degrading nucleases, SDN) and animals (exoribonuclease 2/XRN-2/XRN2). Interference with these miRNA turnover pathways causes excess miRNA activity, consistent with an important contribution to miRNA homeostasis.

Target-mediated protection of endogenous microRNAs in C. elegans.

MicroRNAs (miRNAs) are tightly regulated through transcriptional and posttranscriptional mechanisms, including degradation by nucleases. Here, we report that in C. elegans, target mRNAs can protect their cognate miRNAs from degradation in vivo.

MicroRNAses and the regulated degradation of mature animal miRNAs.

microRNAs (miRNAs) are small noncoding RNAs that regulate numerous target mRNAs through an antisense mechanism. Initially thought to be very stable with half-lives on the order of days, mature miRNAs have recently been shown to be subject to degradation by 'microRNases' (miRNases) in plants (the small RNA degrading nucleases, SDN) and animals (exoribonuclease 2/XRN-2/XRN2). Interference with these miRNA turnover pathways causes excess miRNA activity, consistent with an important contribution to miRNA homeostasis.

Active turnover modulates mature microRNA activity in Caenorhabditis elegans.

MicroRNAs (miRNAs) constitute a large class of regulatory RNAs that repress target messenger RNAs to control various biological processes. Accordingly, miRNA biogenesis is highly regulated, controlled at both transcriptional and post-transcriptional levels, and overexpression and underexpression of miRNAs are linked to various human diseases, particularly cancers. As RNA concentrations are generally a function of biogenesis and turnover, active miRNA degradation might also modulate miRNA accumulation, and the plant 3'-->5' exonuclease SDN1 has been implicated in miRNA turnover.

An RNA-binding respiratory component mediates import of type II tRNAs into Leishmania mitochondria.

Transport of tRNAs across the inner mitochondrial membrane of the kinetoplastid protozoon Leishmania requires interactions with specific binding proteins (receptors) in a multi-subunit complex. The allosteric model of import regulation proposes cooperative and antagonistic interactions between two or more receptors with binding specificities for distinct tRNA families (types I and II, respectively). To identify the type II receptor, the gene encoding RIC8A, a subunit of the complex, was cloned.

A bifunctional tRNA import receptor from Leishmania mitochondria.

In kinetoplastid protozoa, import of cytosolic tRNAs into mitochondria occurs through tRNAs interacting with membrane-bound proteins, the identities of which are unknown. The inner membrane RNA import complex of Leishmania tropica contains multiple proteins and is active for import in vitro. RIC1, the largest subunit of this complex, is structurally homologous to the conserved alpha subunit of F1 ATP synthase.

Mitochondrial differentiation in kinetoplastid protozoa: a plethora of RNA controls.

Differentiation of kinetoplastid protozoa during their complex life cycles is accompanied by stepwise changes in mitochondrial functions. Recent studies have begun to reveal multilevel post-transcriptional regulatory mechanisms by which the expression of the nuclear and mitochondrially encoded components of respiratory enzymes is coordinated, as well as the identities of some general and gene-specific factors controlling mitochondrial differentiation.

Allosteric regulation of tRNA import: interactions between tRNA domains at the inner membrane of Leishmania mitochondria.

Import of nucleus-encoded tRNAs into the mitochondria of the kinetoplastid protozoon Leishmania involves recognition of specific import signals by the membrane-bound import machinery. Multiple signals on different tRNA domains may be present, and further, importable RNAs interact positively (Type I) or negatively (Type II) with one another at the inner membrane in vitro. By co-transfection assays, it is shown here that tRNA(Tyr) (Type I) transiently stimulates the rate of entry of tRNA(Ile) (Type II) into Leishmania mitochondria in transfected cells, and conversely, is inhibited by tRNA(Ile).

"Ping-pong" interactions between mitochondrial tRNA import receptors within a multiprotein complex.

The mitochondrial genomes of a wide variety of species contain an insufficient number of functional tRNA genes, and translation of mitochondrial mRNAs is sustained by import of nucleus-encoded tRNAs. In Leishmania, transfer of tRNAs across the inner membrane can be regulated by positive and negative interactions between them. To define the factors involved in such interactions, a large multisubunit complex (molecular mass, approximately 640 kDa) from the inner mitochondrial membrane of the kinetoplastid protozoon Leishmania, consisting of approximately 130-A particles, was isolated.

Mitochondrial RNA import in Leishmania tropica: aptamers homologous to multiple tRNA domains that interact cooperatively or antagonistically at the inner membrane.

A large number of cytoplasmic tRNAs are imported into the kinetoplast-mitochondrion of Leishmania by a receptor-mediated process. To identify the sequences recognized by import receptors, mitochondria were incubated with a combinatorial RNA library. Repeated cycles of amplification of the imported sequences (SELEX) resulted in rapid selection of several import aptamers containing sequence motifs present in the anticodon arm, the D arm, the V-T region, and acceptor stem of known tRNAs, confirming or suggesting the presence of import signals in these domains.