| 2014 |
FAM98B is a component of the human tRNA splicing ligase complex (tRNA-LC), which contains RTCB (HSPC117) as the catalytic subunit. FAM98B was identified as part of this multimeric complex required for tRNA splicing and RNA ligation. |
Biochemical purification and identification of complex components; co-purification with RTCB |
Nature |
High |
24870230
|
| 2014 |
FAM98B co-purifies with DDX1, HSPC117 (RTCB), and hCLE (C14orf166) in both nuclear and cytoplasmic fractions, forming a complex that shuttles between nucleus and cytoplasm. Nuclear import of FAM98B requires active transcription, and silencing of hCLE downregulates nuclear and cytosolic accumulation of FAM98B. |
Nuclear/cytoplasmic fractionation, co-immunoprecipitation, photoactivatable GFP-hCLE live imaging, RNA silencing |
PloS one |
Medium |
24608264
|
| 2019 |
FAM98B associates with hCLE (C14orf166), DDX1, and HSPC117 in a cap-binding complex; all four proteins bind cap analog-containing resins. This complex modulates mRNA translation, as hCLE silencing reduces accumulation of all four proteins and decreases mRNA translation. |
Cap analog affinity resin pulldown, competition/elution experiments, RNA silencing, polysome analysis |
Frontiers in physiology |
Medium |
30833903
|
| 2016 |
FAM98B, along with its structural homolog FAM98A, forms a novel complex with DDX1 and C14orf166 that is required for PRMT1 expression in colorectal cancer cells. Knockdown of FAM98B suppresses cellular proliferation and colony formation. Knockdown of both FAM98A and FAM98B together does not cause additional reduction compared to single knockdowns, indicating they function in the same pathway axis. |
Co-immunoprecipitation, shRNA knockdown, cell proliferation and colony formation assays, epistasis by double knockdown |
The international journal of biochemistry & cell biology |
Medium |
28040436
|
| 2021 |
The core of the human tRNA-LC is assembled from RTCB and the C-terminal alpha-helical regions of DDX1, CGI-99, and FAM98B, all of which are required for complex integrity. CGI-99 and FAM98B associate via their N-terminal domains to form a stable subcomplex. Crystal structure of GMP-bound RTCB reveals divalent metal coordination in the active site. |
Biochemical analysis of inter-subunit interactions, crystal structure determination of RTCB and CGI-99 N-terminal domain, deletion mutagenesis |
eLife |
High |
34854379
|
| 2025 |
FAM98B contains the most glycine-rich intrinsically disordered region (IDR) in the human proteome. In GGC repeat expansion disorders, polyglycine aggregates sequester and deplete FAM98B through this glycine-rich IDR, disrupting tRNA-LC function and tRNA processing. Fam98b depletion in adult mice causes progressive motor coordination deficits and hindbrain pathology. |
Biochemical aggregation assays, patient tissue analysis, FISH for tRNA splicing intermediates, in vivo mouse knockdown with behavioral and histological readouts |
Science (New York, N.Y.) |
High |
40674500
|
| 2020 |
FAM98B binds to the major allele of the rs11466313 variant in the 5' regulatory region of TGFB1; knockdown of FAM98B attenuates the enhanced TGFB1 promoter activity driven by the major allele, indicating FAM98B functions as a transcriptional activator of TGFB1 through this regulatory element. |
DNA pull-down assay, mass spectrometry identification, luciferase reporter assay, siRNA knockdown |
Breast cancer research and treatment |
Medium |
32757134
|
| 2025 |
FAM98B depletion by shRNA in osteoclast precursors specifically disrupts lysosome trafficking and bone resorption in osteoclasts, with phenotypes similar to FAM98A knockdown. In Fam98a-null osteoclasts, increased Fam98b expression occurs as compensation. |
shRNA knockdown in osteoclast precursors, lysosomal trafficking assays, bone resorption assays, qPCR for compensatory expression |
Biology |
Medium |
39857276
|
| 2025 |
Cryo-EM structure of the human tRNA-LC reveals that CGI-99, DDX1, and FAM98B form an alpha-helical bundle contacting RTCB. FAM98B and CGI-99 form an intricately co-folded heterodimer that clamps Ashwin in a pincer-like structure. FAM98A and FAM98C can substitute for FAM98B to underpin compositionally distinct RTCB-containing complexes that lack Ashwin and may have distinct cellular functions. |
Cryo-EM structure determination at atomic resolution, structure-based mutagenesis, interaction analysis |
bioRxivpreprint |
High |
bio_10.1101_2025.08.01.668197
|
| 2025 |
Three forms of the tRNA-LC exist depending on which FAM98 paralog (FAM98A, FAM98B, or FAM98C) is incorporated. Ashwin interacts exclusively with the FAM98B-containing complex, enabling nuclear localization of this specific tRNA-LC form for tRNA biogenesis. The FAM98B-tRNA-LC is thus the nuclear form required for pre-tRNA splicing, while FAM98A/C-containing complexes remain cytoplasmic for XBP1 mRNA splicing during UPR. |
Co-immunoprecipitation, NLS disruption mutagenesis, subcellular fractionation, tRNA splicing intermediate accumulation assay, rescue experiments with RTCB-NLS fusion |
bioRxivpreprint |
High |
bio_10.1101_2025.08.01.668163
|
| 2025 |
Cryo-EM structure of the five-subunit Danio rerio tRNA ligase complex shows that the DDX1 helicase module is mobile and can modulate the activity of RTCB. Chemical crosslinking confirmed specific RTCB residue involvement in RNA binding. |
Cryo-EM structure determination, thiol-based chemical crosslinking |
The Journal of biological chemistry |
Medium |
40220997
|