Biology subjects

Bernhard, H.

Publications and source records attributed to Bernhard, H..

3 recordsLinked to original sources

bioRxiv2024

Structural basis of Spliced Leader RNA recognition by the Trypanosoma brucei cap-binding complex

Kinetoplastids are a clade of eukaryotic protozoans that include human parasitic pathogens like trypanosomes and Leishmania species. In these organisms, protein-coding genes are transcribed as polycistronic pre-mRNAs, which need to be processed by the coupled action of trans-splicing and polyadenylation to yield monogenic mature mRNAs. During trans-splicing, a universal RNA sequence, the spliced leader RNA (SL RNA) mini-exon, is added to the 5-end of each mRNA. The 5-end of this mini-exon carries a hypermethylated cap structure and is bound by a trypanosomatid-specific cap-binding complex (CBC). The function of three of the kinetoplastid CBC subunits is unknown, but an essential role in cap binding and trans-splicing has been suggested. Here, we report cryo-EM structures that reveal the molecular architecture of the Trypanosoma brucei CBC (TbCBC) complex. We find that TbCBC interacts with two distinct features of the SL RNA. The TbCBP20 subunit interacts with the m7G cap while TbCBP66 recognizes double-stranded portions of the SL RNA. Our findings pave the way for future research on mRNA maturation in kinetoplastids. Moreover, the observed structural similarities and differences between TbCBC and the mammalian cap-binding complex will be crucial for considering the potential of TbCBC as a target for anti-trypanosomatid drug development. HighlightsO_LICryo-EM reveals the molecular architecture of the tetrameric Trypanosoma brucei cap-binding complex (TbCBC). C_LIO_LITbCBP110 is the kinetoplastid homolog of mammalian CBP80 and forms the scaffold for TbCBP20. C_LIO_LITbCBC has a bilobal architecture with TbCBP30 bridging the flexibly attached TbCBP66 subunit and the TbCBP20-TbCBP110 core complex. C_LIO_LITbCBC recognizes the m7G RNA cap independent of the other trypanosomatid-specific cap4 methylations. C_LIO_LIThe TbCBP66 subunit contains a binding site for dsRNA, augmenting the affinity of TbCBC for the SL RNA. C_LI

molecular biology↗

bioRxiv2022

Spatiotemporal patterns of sleep spindle activity in human anterior thalamus and cortex

Sleep spindles (8 - 16 Hz) are transient electrophysiological events during non-rapid eye movement sleep. While sleep spindles are routinely observed in the cortex using scalp electroencephalography (EEG), recordings of their thalamic counterparts have not been widely studied in humans. Based on a few existing studies, it has been hypothesized that spindles occur as largely local phenomena. We investigated intra-thalamic and thalamocortical spindle co-occurrence, which may underlie thalamocortical communication. We obtained scalp EEG and thalamic recordings from 7 patients that received bilateral deep brain stimulation (DBS) electrodes to the anterior thalamus for the treatment of drug resistant focal epilepsy. Spindles were categorized into subtypes based on their main frequency (i.e., slow (10{+/-}2 Hz) or fast (14{+/-}2 Hz)) and their level of thalamic involvement (spanning one channel, or spreading uni- or bilaterally within the thalamus). For the first time, we contrasted observed spindle patterns with permuted data to estimate random spindle co-occurrence. We found that multichannel spindle patterns were systematically coordinated at the thalamic and thalamocortical level. Importantly, distinct topographical patterns of thalamocortical spindle overlap were associated with slow and fast subtypes of spindles. These observations provide further evidence for coordinated spindle activity in thalamocortical networks. HighlightsO_LISleep spindles were measured in human anterior thalamus and on the scalp C_LIO_LIBoth fast and slow spindles occurred in the anterior thalamus C_LIO_LI> 25% of spindles spanned multiple channels in thalamus and cortex C_LIO_LIA novel statistical approach confirmed that spindle co-occurrences were not random C_LIO_LICortical spindle patterns depended on thalamic involvement and spindle frequency C_LI

neuroscience↗

bioRxiv2021

Predicting mind wandering episodes quarter hours in advances from EEG

Whether spontaneous or induced by a tedious task, the transition from a focused mental state to mind wandering is a complex one, possibly involving adjacent mental states and extending over minutes or even hours. This complexity cannot be captured by relying solely on subjective reports of mind wandering. To characterize the transition in a mind-wandering-inducing tone counting task, in addition we collected subjective reports of thought generation along with task performance as a measure of cognitive control and EEG measures, namely auditory probe evoked potentials (AEP) and ongoing 8-12Hz alpha-band amplitude. We analyzed the cross-correlations between timeseries of these observations to reveal their contributions over time to the occurrence of task-focused and mind-wandering states. Thought generation and cognitive control showed overall a yoked dynamics, in which thought production increased when cognitive control decreased. Prior to mind wandering however, they became decoupled after transient increases in cognitive control-related alpha amplitude. The decoupling allows transitory mental states beyond the unidimensional focused/wandering continuum. Time lags of these effects were on the order of several minutes, with 4-10 minutes for that of alpha amplitude. We discuss the implications for mind wandering and related mental states, and for mind-wandering prediction applications.

neuroscience↗