The L1TD1 Protein Interactome Reveals the Importance of Post-transcriptional Regulation in Human Pluripotency

Abstract

SummaryThe RNA-binding protein L1TD1 is one of the most specific and abundant proteins in pluripotent stem cells and is essential for the maintenance of pluripotency in human cells. Here, we identify the protein interaction network of L1TD1 in human embryonic stem cells (hESCs) and provide insights into the interactome network constructed in human pluripotent cells. Our data reveal that L1TD1 has an important role in RNA splicing, translation, protein traffic, and degradation. L1TD1 interacts with multiple stem-cell-specific proteins, many of which are still uncharacterized in the context of development. Further, we show that L1TD1 is a part of the pluripotency interactome network of OCT4, SOX2, and NANOG, bridging nuclear and cytoplasmic regulation and highlighting the importance of RNA biology in pluripotency.

Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy

“…Similar to KANK4 , L1TD1 is only weakly expressed in the corneal endothelium (Supplementary Data 1). L1TD1 is a RNA-binding protein involved in preserving pluripotency of stem cells via post-transcriptional regulation, showing high expression in pluripotent cells31. Functions of moieties that interact with L1TD1 can be divided into three categories: RNA post-transcriptional modification, protein synthesis and gene expression.…”

“…Functions of moieties that interact with L1TD1 can be divided into three categories: RNA post-transcriptional modification, protein synthesis and gene expression. Emani et al 31. reported that LAMC1 is involved in protein synthesis under control of L1TD1 .…”

Post-transcriptional regulation of the pluripotent state

“…It is an RBP that interacts with LIN 28 via RNA, and may regulate pluripotency gene expression post-transcriptionally [71]. Further analysis of L1TD1 interactome revealed that it indeed binds to many RNA processing factors, adding additional support for its role in RNA regulation in pluripotent stem cells [72].…”

Proteomics-Based Analysis of Protein Complexes in Pluripotent Stem Cells and Cancer Biology

“…The high levels of L1TD1 has been identified in ESCs and is involved in maintenance of human ES cells pluripotency. The AP-MS approach identified 306 proteins in the interactome of L1TD1 and several of them were known to be shared with Oct4, Sox2 and Nanog interactomes [ 81 ]. This study validated several of the identified interactors of L1TD1 including CTNNB1, DDX3X, DHX9, ELAVL1, IGF2BP1, IGF2BP3, KHDRBS1, KPNA2, PABPC1, and PARP1.…”