Chapter 4 Explore post-transcriptional gene regulation

So as to highlight genes that are potentially affected by post-transcriptional gene regulation, we filtered genes on several parameters:

• Similar transcripts level in epithelium and fiber: genes with RNA level > 1.33 FC were excluded.

• Distinct protein levels: minimum 2.15 FC of differential expression in iBAQ, LFQ and intensity values to conserve genes.

• Non-null protein expression: proteins with iBAQ or LFQ or intensity values null in both tissues were excluded.

Using this approach we identified 493 distinct genes.

324 proteins enriched in epithelium; 169 enriched in fibers.

4.1 Assessing the relevance of identified genes

4.1.1 Connection to eye’s development: associated phenotype

With a simple approach, using Ensembl database, we looked for eye’s related phenotypes associated with our genes.

Interestingly, we found 39 genes amongst our list of 493 potentially post tx regulated genes.

4.2 Candidates ptx regulated genes with eye’s related phenotypes

Here is a summary table for genes identified and eye’s related phenotype:

Table 4.1: Candidate post-transcriptionnaly-regulated genes with eye’s related phenotype

Tissue	MGI symbol	Associated phenotype
epithelium	Adam17	abnormal anterior eye segment morphology, abnormal eye morphology, abnormal eyelid margin morphology, abnormal retina morphology, anophthalmia, cataract, eye opacity, eyelids open at birth, failure of eyelid fusion, microphthalmia, vacuolated lens
epithelium	Adipor1	abnormal retinal outer nuclear layer morphology, decreased total retina thickness, abnormal retina morphology
fiber	Agtpbp1	abnormal eye electrophysiology, abnormal retinal inner plexiform layer morphology, abnormal retinal layer morphology, abnormal retinal outer nuclear layer morphology, abnormal retinal photoreceptor layer morphology, abnormal retinal rod cell morphology, retinal degeneration, retinal photoreceptor degeneration, thin retinal outer nuclear layer
epithelium	Anxa3	abnormal lens morphology, abnormal retinal blood vessel morphology
epithelium	Ascc2	abnormal retinal inner nuclear layer morphology
epithelium	Bckdha	microphthalmia
fiber	Bloc1s5	abnormal eye pigmentation, abnormal retinal pigment epithelium morphology, decreased eye pigmentation
fiber	Clcn7	abnormal retinal pigment epithelium morphology, retinal degeneration, thin retinal inner nuclear layer, thin retinal outer nuclear layer
fiber	Clec16a	narrow eye opening
epithelium	Fkbp8	anophthalmia, microphthalmia
epithelium	Foxk2	abnormal retinal blood vessel morphology
fiber	Golga1	cataract
fiber	H13	abnormal eye muscle morphology, persistent dorsal ophthalmic artery
epithelium	Hmbs	abnormal lens morphology, abnormal vitreous body morphology
epithelium	Hmx1	microphthalmia
fiber	Ift172	anophthalmia
epithelium	Ift57	ocular hypotelorism
epithelium	Itgb5	abnormal eye morphology, abnormal retina morphology
epithelium	Lrrc8a	abnormal eye morphology, anophthalmia
fiber	Mthfr	exophthalmos
epithelium	Myo5a	abnormal eye blink conditioning behavior
epithelium	Nectin1	abnormal anterior eye segment morphology, abnormal lens morphology, abnormal retinal layer morphology, abnormal vitreous body morphology, eyelids open at birth, failure of eyelid fusion, microphthalmia
epithelium	Nid1	abnormal lens morphology
epithelium	Nmnat1	abnormal retina morphology, abnormal retinal inner nuclear layer morphology, abnormal retinal vasculature morphology, decreased total retina thickness, disorganized retinal inner nuclear layer, retinal degeneration, retinal outer nuclear layer degeneration, retinal photoreceptor degeneration, retinal pigment epithelium atrophy, thin retinal inner nuclear layer, thin retinal outer nuclear layer
epithelium	Oplah	abnormal lens morphology, cataract
epithelium	Pde6d	abnormal eye electrophysiology, abnormal retinal rod cell morphology, abnormal retinal rod cell outer segment morphology, decreased retinal cone cell number, retinal degeneration, thin retinal outer nuclear layer
epithelium	Pitx3	anophthalmia, abnormal anterior eye segment morphology, abnormal eye distance/ position, abnormal eye morphology, abnormal lens development, abnormal ocular fundus morphology, abnormal posterior eye segment morphology, abnormal retina morphology, eyelids fail to open, fused cornea and lens, microphthalmia
epithelium	Rab35	abnormal lens morphology, cataract
fiber	Rab3gap2	narrow eye opening
fiber	Rundc1	abnormal eye morphology, abnormal eye muscle morphology
epithelium	Snx17	anophthalmia
epithelium	Sorbs2	abnormal retina morphology, abnormal retinal pigmentation
epithelium	Sort1	abnormal eye physiology, abnormal retinal ganglion cell morphology
epithelium	Sparc	abnormal eye morphology, abnormal lens morphology, cataract, abnormal lens capsule morphology, abnormal lens epithelium morphology, abnormal lens fiber morphology, abnormal retinal layer morphology, cortical cataracts, eye inflammation, posterior subcapsular cataracts, retinal degeneration, retinal detachment, ruptured lens capsule, subcapsular cataracts, vitreous body inflammation
epithelium	Timm50	abnormal retinal outer nuclear layer morphology
fiber	Trim2	decreased retinal ganglion cell number, retinal ganglion cell degeneration, thin retinal inner nuclear layer, thin retinal outer plexiform layer
epithelium	Wdsub1	abnormal retinal blood vessel morphology, abnormal vitreous body morphology, decreased total retina thickness
fiber	Ydjc	abnormal retina morphology, abnormal retinal pigmentation

4.3 Biological process

The following wordcloud was produced using annotations of biological processes for the genes listed in the previous table. Colour and size of words are linked to their frequency of occurence (minimal occurence=2).