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Suematsu, T.

Publications and source records attributed to Suematsu, T..

3 recordsLinked to original sources

Ripples precede insight in the right human hippocampus

Insight is a sudden transition from uncertainty to awareness of a solution, often preceded by non-conscious processing. Despite the ubiquity of insights in human cognition, the neural mechanisms underlying this pre-conscious restructuring phase remain largely unknown. Recent theoretical frameworks suggest that the hippocampus, through its capacity for rapid associative retrieval and flexible recombination of stored representations, may facilitate the non-conscious exploration that precedes insight. Hippocampal ripples associated with memory replay and consolidation, represent a promising candidate mechanism for this process. We recorded intracranial local field potentials from depth electrodes in the hippocampus of ten patients with drug-resistant epilepsy while they performed non-verbal reasoning tasks. Participants indicated the moment of solution awareness via button press, enabling precise temporal alignment of neural activity to subjective insight. We observed a significant increase in ripple rate during a pre-response window. Critically, this effect was lateralized to the right hippocampus. These findings provide the first direct human electrophysiological evidence linking right-lateralized hippocampal ripples to the non-conscious phase of insight. We propose that right hippocampal ripples support rapid retrieval and flexible recombination of representations, potentially triggering cortical processes that culminate in conscious solution awareness.

neuroscience↗

Pentatricopeptide repeat poly(A) binding protein from mitochondria of trypanosomes

In Trypanosoma brucei, most mitochondrial mRNAs undergo U-insertion/deletion editing, and 3' adenylation and uridylation. The internal sequence changes and terminal extensions are coordinated: Pre-editing addition of the short (A) tail protects the edited transcript against 3'-5' degradation, while post-editing A/U-tailing renders mRNA competent for ribosome recruitment. Participation of a poly(A) binding protein (PABP) in coupling of editing and 3' modification processes has been inferred, but its identity and mechanism of action remained elusive. We report identification of KPAF4, a pentatricopeptide repeat-containing PABP which sequesters the A-tail and impedes exonucleolytic degradation. Conversely, KPAF4 inhibits uridylation of A-tailed transcripts and, therefore, premature A/U-tailing of partially-edited mRNAs. This quality check point prevents translation of incompletely edited mRNAs. Our findings also implicate the RNA editing substrate binding complex (RESC) in mediating the interaction between the 5' end bound pyrophosphohydrolase MERS1 and 3' end associated KPAF4 to enable mRNA circularization. This event is critical for transcript stability during the editing process.

biochemistry↗

Transcription initiation defines kinetoplast RNA boundaries

Mitochondrial genomes are often transcribed into polycistronic primary RNAs punctuated by tRNAs whose excision defines mature RNA boundaries. Although kinetoplast DNA lacks tRNA genes, it is commonly held that monophosphorylated 5'-ends of functional molecules typify precursor partitioning by an unknown endonuclease. To the contrary, we demonstrate that in Trypanosoma brucei individual mRNAs and rRNAs are independently synthesized as 3' extended precursors. The transcription-defined 5' terminus is converted into monophosphorylated state by the 5' pyrophosphohydrolase complex, termed PPsome, which is activated by RNA editing substrate binding complex (RESC). Most guide RNAs lack PPsome recognition sites and, therefore, remain triphosphorylated. We provide evidence that both 5' pyrophosphate removal and 3' adenylation are essential for mRNA stabilization. Furthermore, we uncover a mechanism by which antisense RNA-controlled 3'-5' exonucleolytic trimming defines mRNA 3'-end. We conclude that mitochondrial mRNAs and rRNAs are transcribed and processed as insulated units irrespective of their genomic location.\n\nSignificanceIt is commonly held that in trypanosomes both mitochondrial DNA strands are transcribed into polycistronic precursors. These primary RNAs are presumably partitioned into individual pre-mRNAs by a \"cryptic\" endonuclease. We challenged the polycistronic transcription/ endonuclease model after revealing precursor processing by 3'-5' degradation. This work demonstrates individual transcription of each gene and mRNA 5'-end definition by the first incorporated nucleotide triphosphate. We have uncovered the stabilizing role of 5' triphosphate to monophosphate conversion and identified a protein complex responsible for this reaction. We have discovered antisense noncoding RNA originating near mRNA 3' end and showed that a duplex formation modulates exonuclease activity to delimit the mature 3' end. Collectively, our findings reveal mechanisms by which transcription defines both mRNA termini.

biochemistry↗