The 37-year-old actress had planned to take at least a year off after her son Rocco, who she has with partner Bobby Cannavale, was born in February 2016, but could not turn down the offer to appear in "The Immortal Life of Henrietta Lacks" alongside Winfrey, reported Femalefirst.
I'd just had a child and I was like, 'I don't really want to go back to work. But I read the script and I was like, 'I just...Damn it...I can't say no. I want to be in service of this story ... It's an incredible story. I want to work with (writer) George Wolfe. I want to work with Oprah," Byrne says.
The Australian actress says it was intimidating playing a journalist in front of the 63-year-old celebrity talk show host.
"It was nerve wracking, you know. She's like the ultimate journalist. When you meet someone with such a huge profile it's a strange mix of thinking you know them, and obviously they're a complete stranger, but...There's really not that many people in the world who have her profile.
"She was, to work with though, incredibly professional. She had a huge job. There's no vanity in that performance. She was physically transformed, very emotional, very real, with a responsibility to play this woman," she says.
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