Ragdoll Bites!

Maybe your cat just doesn't like to be picked up and held. Actually until I got Midnight I've never known a cat that liked being held. Lynxx would tolerate it if he had to, but would fight to get down. Luna won't tolerate being held at all, she bites to get down.

Have you taken her to the vet? Maybe something hurts when she get's picked up?

Is it possible that the children were too rough on her at one time? Cats (pedigreed or not) can take a long time to forget a traumatic incident.

It could be possible that she did have some trauma with the kids?? Cats will be unforgiving if they continually get mishandled, even if it is done on accident by small kids. You may just have to love her without having to pick her up and handle her. Do you have any of those tall cat trees in your home with the carpeted perches built in??? She might prefer one of those for a place to rest peacefully and then you wouldn't have to move her off a chair or couch and make her upset. Alot of cats will prefer one of those resting perches and pick that over the chair or couch, especially if it is located near a window. And if you need to move her off of a chair, try to get her to come down on her own by using a treat or a wand toy and then play with her for a few minutes if she obliges your efforts.

are you sure she's purebreed? did you get her from a reputable breeder or some other channel?

i can only go by my experience with my male neutered cat..sometimes too much of a good thing is too much..for instance..when being brushed he loves it but to a degree...after about 15 mins he will start biting me..not tearing the flesh but its like he's telling me that thats enough...
this morning he woke me up cause he wanted to eat..I played with him by putting my hand under the comforter and popping it up..that was fun for a few minutes but then he started biting me..he wanted to eat, not play
I think cats, like humans have a breaking point..if everything they do doesnt get their point across then they revert to instinct

I hope you were not under the assumption that because the Ragdoll had the image of tolerating a lot that the cat would not or should not stand up for herself ?
She is not a toy so make sure your kids leave the cat alone ! No picking up against her will or don't come crying about it when you get scratched or bitten, because mom will tell you off for bothering the cat !

Cats do not "hold grudges" (they are not small humans) , she is probably preemptively defending herself against another kid that she thinks is coming round to bother her.

You write it has gotten to the point where she does not want to be picked up at all, so do not pick her up anymore. Forcing her will not make things better. If she does absolutely need to be moved from somewhere and you'd rather not pick her up, there are other ways to make her do something. Lure her with something she likes. That might be a treat, or a toy, or other things she likes. I have a "door dasher" who will come running when I open (and close) the door to the lobby and a cat who loves to watch the printer, I can lure him to me from anywhere in the house just by the sounds the printer makes when I press the power button.

Playing is OK of course, especially since she seems to be an only cat and indoors, so she needs to be entertained. But she needs to learn that people's bodies/limbs/hands or not toys !
I would try to only let her play with toys that do not require close bodily interaction so she can't hurt you, not even by accident.
So toys on a string/fishing rod toys, toys you throw away for her to fetch, laserpointer, etc, those are safe toys. Try to explain this to the kids too.

She might be ambushing the kids because she is bored and it is fun to hunt them because they will react satisfyingly by screaming and/or running. Make sure she has enough other stimulation. For instance food enrichment, shelves on the walls for her to climb, attract birds to your windows for her to watch, etc.

That's just been my experience. Especially with young kids. I've had three female cats and all were very gentle with kids. Of course I never let the kids play rough either though my first female cat did get a little rough handling from my little brother and sister as they were growing up. I can't say why yours is reacting badly was she dropped or injured maybe? I can see her being warry of kids in that case. Cats are very sensitive to moods and emotions we let off are you stressed when she around? My older cat used to nip me when I would get upset a vet later told me this was his way of calming me down. He hasn't done it lately since the new female cat entered the household....some of his behavior has a changed a bit since then but he does stand there and watch me carefully.

Eh, not so sure that cats have the emotional capacity or attention span to hold a grudge hours later.

They do categorize things as positive or negative, and have a good memory in that regard. I was a dummy and Wesley got caught only for 15-20 seconds in a plastic grocery bag and yet still fears them now, all from one incident.

If repeatedly held too long or awkwardly and not let down when hinting at it (squirms or hanging body down) or squeezed too hard or dropped by an inexperience child, that could classify a kid and/or being picked up into the negative branch and make a kitty defensive from a previous incident. Unlike dogs that may allow someone higher in the pack to hurt them and remain submissive, kitties will usually defend themselves if they feel threatened.

I'd just instruct the kids not to pick her up for now and have them use toys like a Da Bird or little rattle mice or bouncy balls they can throw that she can tear into. Gotta teach that hands and arms are not toys, and give a "tss NO!" if you catch kitty trying to stalk the kids as play-prey.

just another view-you may want to inform the breeder to see if any other cats in the line developed this trait for evaluation of further breeding from the parents. Assuming she was purchased from a reputable breeder and not at a petshop which could explain a bit of the issues at hand too.

I know when we got our first cat he was about 8 yo and i was 14 sister 9 and we got our share of scratches from trying to make him a lapcat but we had never had a cat and only(good-spay/keep inside) experience i was exposed to(different dads and my dads family is the let nature take its course way with animals was my aunts cats all 4 were laid back snuggle bugs! We got a kitten about 8 months later that solved our issue-made first cat angry for awhile but he got over it and sis and I got our lap cat/do anything he didnt care.