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Biology subjects

Kirch, T.

Publications and source records attributed to Kirch, T..

2 recordsLinked to original sources
bioRxiv2026

PABPC1 Modulates Immunoglobulin pre-mRNA Alternative Polyadenylation

Alternative polyadenylation is a mechanism by which cells tune gene expression, and dysregulation can lead to development of disease. PABPC1 has been implicated in poly(A) site selection, but its function in gene regulation remains contradictory and poorly defined. Here, we investigate its role in B cell development, where APA controls immunoglobulin secretion. To define this role, we mapped PABPC1-RNA interactions using CLAP-seq and perturbed PABPC1 expression using a degron based strategy. PABPC1 localizes to the 3UTR in 70% of its gene targets and primarily binds to A-rich regions. Integration with transcriptomic data suggests PABPC1 downregulates 60% of its gene targets. While transcriptome-wide shifts in 3 UTR length were limited, PABPC1 binding was specifically enriched in genes exhibiting significant 3 UTR shortening. Using a foundational genomics model, we find the PAS-proximal region is the most predictive of gene expression within PABPC1 binding sites. Positional analysis revealed PABPC1 localizes closer to the PAS in genes downregulated following depletion. In immunoglobulin transcripts, PABPC1 binds to both secreted and membrane isoforms and is more enriched at the secretory PAS, and depletion modestly alters immunoglobulin expression. Together, our findings demonstrate PABPC1 primarily shortens and downregulates its targets in a context dependent manner. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/720383v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@1a93633org.highwire.dtl.DTLVardef@257f55org.highwire.dtl.DTLVardef@1cad5bcorg.highwire.dtl.DTLVardef@19662fa_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗
bioRxiv2026

Proximity proteomics reveals a role for IFI16 during human coronavirus infection

Viruses rely on the infected host cell to ensure successful replication and propagation of infection. This is achieved through interactions between virus-encoded proteins and proteins expressed in infected cells. All human coronaviruses (HCoVs) encode 16 non-structural proteins (NSPs) which exhibit some level of similarity in identity and function among the HCoVs. To identify host proteins that are potential interacting partners of HCoV NSPs, we utilized split-TurboID along with mass spectrometry and identified IFN-{gamma}-inducible protein-16 (IFI16) as a proximal partner of SARS-CoV-2 NSP8 and NSP10. To investigate the significance of the association between the NSP8/NSP10 complex and IFI16, we utilized CRISPR-Cas9 to knockout and CRISPRi to knockdown IFI16 in A549 cells and demonstrated that loss or reduced expression of IFI16 leads to a decrease in human coronavirus infection. We further demonstrated that there is reduced viral RNA replication and viral protein synthesis upon loss of IFI16. Interestingly, the loss of IFI16 results in reduced expression of type I IFNs. Taken together, these data suggests that IFI16 promotes human coronavirus infection, and the role IFI16 plays in coronavirus replication is independent of its role as a regulator of type I IFN gene expression.

microbiology↗