tRNA-Derived Small RNAs and Their Potential Roles in Cardiac Hypertrophy

Cao, Jun; Cowan, Douglas B.; Wang, Dazhi

doi:10.3389/fphar.2020.572941

Cited by 40 publications

(31 citation statements)

References 196 publications

(421 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Phase separation of tau is particularly efficient upon interaction with tRNA ( 20 ). tiRNAs are fragments of tRNA that are derived upon stress-induced angiogenin cleavage and are known to promote stress granule assembly ( 34 – 37 ). The small size of tiRNA provides a good system for exploring whether RNA sequence or secondary structure might affect tau phase separation.…”

Section: Resultsmentioning

confidence: 99%

TIA1 potentiates tau phase separation and promotes generation of toxic oligomeric tau

Ash

Lei

Shattuck

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Tau protein plays an important role in the biology of stress granules and in the stress response of neurons, but the nature of these biochemical interactions is not known. Here we show that the interaction of tau with RNA and the RNA binding protein TIA1 is sufficient to drive phase separation of tau at physiological concentrations, without the requirement for artificial crowding agents such as polyethylene glycol (PEG). We further show that phase separation of tau in the presence of RNA and TIA1 generates abundant tau oligomers. Prior studies indicate that recombinant tau readily forms oligomers and fibrils in vitro in the presence of polyanionic agents, including RNA, but the resulting tau aggregates are not particularly toxic. We discover that tau oligomers generated during copartitioning with TIA1 are significantly more toxic than tau aggregates generated by incubation with RNA alone or phase-separated tau complexes generated by incubation with artificial crowding agents. This pathway identifies a potentially important source for generation of toxic tau oligomers in tau-related neurodegenerative diseases. Our results also reveal a general principle that phase-separated RBP droplets provide a vehicle for coassortment of selected proteins. Tau selectively copartitions with TIA1 under physiological conditions, emphasizing the importance of TIA1 for tau biology. Other RBPs, such as G3BP1, are able to copartition with tau, but this happens only in the presence of crowding agents. This type of selective mixing might provide a basis through which membraneless organelles bring together functionally relevant proteins to promote particular biological activities.

show abstract

Section: Resultsmentioning

confidence: 99%

TIA1 potentiates tau phase separation and promotes generation of toxic oligomeric tau

Ash

Lei

Shattuck

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Finally of note, tRFs unquestionably participate in more than viral defense. In eukaryotes, an array of regulatory roles for tRFs have been reported involving: transcription, translation, apoptosis, cellular proliferation / differentiation, RNAi, intercellular communication, epigenetics, retrotransposon restriction, etc 39 . While several bacterial tRF characterizations have also been reported [40][41][42] , to date, the functions tRFs serve in prokaryotes are far less well described.…”

Section: Discussionmentioning

confidence: 99%

Salmonella Outer Membrane Vesicles contain tRNA Fragments (tRFs) that Inhibit Bacteriophage P22 infection

Houserova

Huang

Kasukurthi

et al. 2021

Preprint

View full text Add to dashboard Cite

Salmonella Outer Membrane Vesicles (OMVs) were recently shown to inhibit P22 bacteriophage infection. Furthermore, despite there being several published reports now independently describing (1) the marked prevalence of tRFs within secreted vesicle transcriptomes and (2) roles for specific tRFs in facilitating/inhibiting viral replication, there have been no examinations of the effects of vesicle-secreted tRFs on viral infection reported to date. Notably, while specific tRFs have been reported in a number of bacteria, the tRFs expressed by salmonellae have not been previously characterized. As such, we recently screened small RNA-seq datasets for the presence of recurrent, specifically excised tRFs and identified 31 recurrent, relatively abundant tRFs expressed by Salmonella enterica serovar Typhimurium (SL1344). What’s more, we find S. Typhimurium OMVs contain significant levels of tRFs highly complementary to known Salmonella enterica-infecting bacteriophage with 17 of 31 tRFs bearing marked complementarity to at least one known Salmonella enterica-infecting phage (averaging 97.4% complementarity over 22.9 nt). Most notably, tRNA-Thr-CGT-1-1, 44-73, bears 100% sequence complementary over its entire 30 nt length to 29 distinct, annotated Salmonella enterica-infecting bacteriophage including P22. Importantly, we find inhibiting this tRF in secreted OMVs improves P22 infectivity in a dose dependent manner whereas raising OMV tRF levels conversely inhibits P22 infectivity. Furthermore, we find P22 phage pre-incubation with OMVs isolated from naïve, control SL1344 S. Typhimurium, successfully rescues the ability of S. Typhimurium transformed with a specific tRNA-Thr-CGT-1-1, 44-73 tRF inhibitor to defend against P22. Collectively, these experiments confirm tRFs secreted in S. Typhimurium OMVs are directly involved with and required for the ability of OMVs to defend against bacteriophage predation. As we find the majority of OMV tRFs are highly complementary to an array of known Salmonella enterica-infecting bacteriophage, we suggest OMV tRFs may primarily function as a broadly acting, previously uncharacterized innate antiviral defense.

show abstract

“…Next, the pre-tRNA is exported to the cytoplasm by Exportin-5 or Exportin-T, where the pre-tRNA is cleaved by Dicer or angiogenin (ANG): Dicer cleaves the D-loop, both Dicer and ANG cleave the T-loop, and ANG cleaves anticodon loop. The cleaved tRNA interacts with AGO to form a mature miRNA complex involved in a variety of biological functions (Cao et al, 2020). In addition, the lupus autoantigen (LA) is a conserved nuclear RNA-binding factor.…”

Section: Micrornas From Transfer Rnasmentioning

confidence: 99%

MicroRNAs Regulating Mitochondrial Function in Cardiac Diseases

et al. 2021

View full text Add to dashboard Cite

Mitochondria are the key organelles that supply cellular energy. As the most active organ in the body, the energy required to maintain the mechanical function of the heart requires a high quantity of high-quality mitochondria in cardiomyocytes. MicroRNAs (miRNAs) are single-stranded noncoding RNAs, approximately 22 nt in length, which play key roles in mediating post-transcriptional gene silencing. Numerous studies have confirmed that miRNAs can participate in the occurrence and development of cardiac diseases by regulating mitochondrial function-related genes and signaling pathways. Therefore, elucidating the crosstalk that occurs between miRNAs and mitochondria is important for the prevention and treatment of cardiac diseases. In this review, we discuss the biogenesis of miRNAs, the miRNA-mediated regulation of major genes involved in the maintenance of mitochondrial function, and the effects of miRNAs on mitochondrial function in cardiac diseases in order to provide a theoretical basis for the clinical prevention and treatment of cardiac disease and the development of new drugs.

show abstract

tRNA-Derived Small RNAs and Their Potential Roles in Cardiac Hypertrophy

Cited by 40 publications

References 196 publications

TIA1 potentiates tau phase separation and promotes generation of toxic oligomeric tau

TIA1 potentiates tau phase separation and promotes generation of toxic oligomeric tau

Salmonella Outer Membrane Vesicles contain tRNA Fragments (tRFs) that Inhibit Bacteriophage P22 infection

MicroRNAs Regulating Mitochondrial Function in Cardiac Diseases

Contact Info

Product

Resources

About