Biology subjects

Jakobsen, L.

Publications and source records attributed to Jakobsen, L..

3 recordsLinked to original sources

bioRxiv2025

Molecular basis of polyadenylated RNA fate determination in the nucleus

Eukaryotic genomes generate a plethora of polyadenylated (pA+) RNAs1,2, that are packaged into ribonucleoprotein particles (RNPs). To ensure faithful gene expression, functional pA+ RNPs, including protein-coding RNPs, are exported to the cytoplasm, while transcripts within non-functional pA+ RNPs are degraded in the nucleus1-4. How cells distinguish these opposing fates remains unknown. The DExD-box ATPase UAP56/DDX39B is a central component of functional pA+ RNPs, promoting their docking to the nuclear pore complex (NPC)-anchored transcription and export complex 2 (TREX-2) (ref.5,6), which triggers transcript release from UAP56 to facilitate export (ref.7,8). Here, we uncover that the Poly(A) tail exosome targeting (PAXT) connection9 harbors its own TREX-2-like module, which releases pA+ RNAs from UAP56 for decay by the nuclear exosome. The core of this module consists of a LENG8-PCID2-SEM1 (LENG8-PS) trimer, which we show is structurally and functionally equivalent to the central GANP-PCID2-SEM1 (GANP-PS) trimer of TREX-2. Mutagenesis and transcriptomic data demonstrate that the nuclear fate of pA+ RNPs is governed by the contending actions of nucleoplasmic PAXT and NPC-associated TREX-2, which interpret RNA-bound UAP56 as a signal for RNA decay or export, respectively. As RNA targets of PAXT are generally short and intron-poor, we propose an overall model for pA+ RNP fate determination, whereby the distinct sub-nuclear localizations of PAXT and TREX-2 govern the degradation of short non-functional pA+ RNAs while allowing export of their longer and functional counterparts.

molecular biology↗

bioRxiv2024

3D photogrammetry as a low cost, portable and noninvasive method for acoustic modeling of hearing

O_LIAnimals with specialized hearing such as bats utilize the directionality of their hearing for complicated tasks such as navigation and foraging. The directionality of hearing can be described through the head related transfer function (HRTF). Current state of the art for obtaining the HRTF involves either direct measurement with a microphone at the eardrum, or a CT (micro computed tomography) scan to create a 3D model of the head for acoustic modelling. Both methods usually involve dead animals. C_LIO_LIWe developed a 3D photogrammetry approach to create scaled 3D models of bats with sufficient detail to simulate the HRTF using the boundary element method (BEM). We designed a setup of 28 cameras to obtain 3D models and HRTF from live awake bats. We directly compare the mesh models generated by our photogrammetry method and from CT scans as well as the simulated HRTFs from both with measurements using an in-ear microphone. C_LIO_LIGeometries of the mesh models match well between photogrammetry and CT, but with increasing errors where line of sight is compromised for photogrammetry. The resulting HRTFs are in great agreement when comparing CT and in-ear measurements to photogrammetry (correlation coefficients above 0.6). The 3D model and simulated HRTF of the live and awake bat likewise aligns well to the results from the deceased animals. C_LIO_LIPhotogrammetry is a viable alternative to CT scans for the generation of surface models of small animals. These models allow numerical modelling of HRTFs at biologically relevant frequencies. Moreover, photogrammetry allows for model generation and subsequent HRTF simulation of live, awake animals, abolishing the need for euthanasia and anesthesia. It paves the way for large scale acquisition of 3D models for various purposes including HRTFs. C_LI

animal behavior and cognition↗

bioRxiv2023

Dual agonistic and antagonistic roles of ZC3H18 provides for co-activation of distinct nuclear RNA decay pathways

The RNA exosome is a versatile ribonuclease. In the nucleoplasm of mammalian cells, it is assisted by its adaptors the Nuclear EXosome Targeting (NEXT) complex and the PolyA eXosome Targeting (PAXT) connection. Via its association with the ARS2 and ZC3H18 proteins, NEXT/exosome is recruited to capped and short unadenylated transcripts. Conversely, PAXT/exosome was considered to target longer and adenylated substrates via their poly(A) tails. Here, mutational analysis of the core PAXT component ZFC3H1 uncovers a separate branch of the PAXT pathway, which targets short adenylated RNAs and relies on a direct ARS2-ZFC3H1 interaction. We further demonstrate that similar acidic-rich short linear motifs of ZFC3H1 and ZC3H18 compete for a common ARS2 epitope. Consequently, while promoting NEXT function, ZC3H18 antagonizes PAXT activity. We suggest that this unprecedented organization of RNA decay complexes provides co-activation of NEXT and PAXT at loci with abundant production of short exosome substrates.

molecular biology↗