FAM32A

Case study 1: Xiechao Zhan, 2022

Pre-mRNA splicing involves two sequential reactions: branching and exon ligation. The C complex after branching undergoes remodeling to become the C∗ complex, which executes exon ligation. Here, the researchers report cryo-EM structures of two intermediate human spliceosomal complexes, pre-C∗-I and pre-C∗-II, both at 3.6 Å. In both structures, the 3' splice site is already docked into the active site, the ensuing 3' exon sequences are anchored on PRP8, and the step II factor FAM192A contacts the duplex between U2 snRNA and the branch site. In the transition of pre-C∗-I to pre-C∗-II, the step II factors Cactin, FAM32A, PRKRIP1, and SLU7 are recruited. Notably, the RNA helicase PRP22 is positioned quite differently in the pre-C∗-I, pre-C∗-II, and C∗ complexes, suggesting a role in 3' exon binding and proofreading. Together with information on human C and C∗ complexes, the studies recapitulate a molecular choreography of the C-to-C∗ transition, revealing mechanistic insights into exon ligation.

Fig1. Overall structures of the human pre-C∗-I and pre-C∗-II complexes.

Fig2. A close-up view on the accommodation of 3′SS and 3′ exon in pre-C∗-II.

Case study 2: Sebastian M Fica, 2019

During exon ligation, the Saccharomyces cerevisiae spliceosome recognizes the 3'-splice site (3'SS) of precursor messenger RNA (pre-mRNA) through non-Watson-Crick pairing with the 5'SS and the branch adenosine, in a conformation stabilized by Prp18 and Prp8. Here the researchers present the 3.3-angstrom cryo-electron microscopy structure of a human postcatalytic spliceosome just after exon ligation. The 3'SS docks at the active site through conserved RNA interactions in the absence of Prp18. Unexpectedly, the metazoan-specific FAM32A directly bridges the 5'-exon and intron 3'SS of pre-mRNA and promotes exon ligation, as shown by functional assays. CACTIN, SDE2, and NKAP-factors implicated in alternative splicing-further stabilize the catalytic conformation of the spliceosome during exon ligation. Together these four proteins act as exon ligation factors. The study reveals how the human spliceosome has co-opted additional proteins to modulate a conserved RNA-based mechanism for 3'SS selection and to potentially fine-tune alternative splicing at the exon ligation stage.

Fig3. FAM32A promotes exon ligation.

Fig4. FAM32A cross-links to the 5´-exon.

Fig1. A working model for the C-to-C∗ transition. (Xiechao Zhan, 2022)

Fig2. Model for the action of exon ligation factors in metazoans. (Sebastian M Fica, 2019)

FAM32A involved in several pathways and played different roles in them. We selected most pathways FAM32A participated on our site, such as , which may be useful for your reference. Also, other proteins which involved in the same pathway with FAM32A were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

FAM32A has several biochemical functions, for example, poly(A) RNA binding, protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by FAM32A itself. We selected most functions FAM32A had, and list some proteins which have the same functions with FAM32A. You can find most of the proteins on our site.

FAM32A has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with FAM32A here. Most of them are supplied by our site. Hope this information will be useful for your research of FAM32A.

CWC22; NSFL1C; CCDC22; Ccdc12